Medstudy im core curriculum, 16e book 3 cardiology & rheumatology unitedvrg by Amran Hajjaj

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MedStudyÂ® INTERNAL MEDICINE REVIEW

SIXTEENTH

EDITION

CURRICULUM

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Book 3 of 5

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Topics in this volume:

Cardiology

Rheumatology

Robert A. Hannaman, MD Editor in Chief

Disclaimers

NOTICE: Medicine and accepted standards of care are constantly changing. We at MedStudy do our best to review and include in this publication accurate discussions of the standards of care and methods of diagnosis. However, the editor in chief, the reviewers, the section editors, the publisher, and all other parties involved with the preparation and publication of this work do not guarantee that the information contained herein is in every respect accurate or complete. MedStudy further disclaims any and all liability for damages and claims that may result from the use of information or viewpoints presented. We recommend that you confirm the material with current sources of medical knowledge whenever considering presentations or treating patients.

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ABIM: For over 20 years, MedStudy has excelled in determining and teaching what a clinically competent Internal Medicine physician should know. The American Board of Internal Medicine (ABIM) tests this exact same pool of knowledge. MedStudy's expertise, demonstrated by the superb pass rate of those who use it in their studies, is in the actual "teaching" of this knowledge in a clear, learner-friendly manner

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that results in a stronger knowledge base, improved clinical skills, and better Board results. Although what we teach is in sync with what the Board tests, MedStudy has no affiliation with the ABIM, and our authors, editors, and reviewers have no access to ABIM exam content. Our material is developed as original work by MedStudy physician authors, with additional input from expert contributors, based on their extensive backgrounds in professional medical education. This content is designed to include subject matter typically tested in certification and recertification exams as outlined in the ABIM's publicly available exam blueprints but makes no use of, and divulges no details of, ABIM's proprietary exam content.

A note on editorial style: MedStudy uses a standardized approach to the naming of diseases. The previous method of naming was to use the possessive form that adds "'s" to the names of diseases

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and disorders, such as Lou Gehrig's disease, Klinefelter's syndrome, and others. In MedStudy material, you will see the non-possessive form when the proper name is followed by a common noun; e.g., ''This patient would warrant workup for Crohn disease." Exceptions to the possessive form

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include Bell's palsy and Still's murmur. The possessive form will be used, however, when an entity is referred to solely by its proper name without a following common noun; e.g., "The symptoms are classic for Crohn's." The AMA Manual of Style, JAMA®, and Scientific Style and Format are among the publications that promote and use the non-possessive form.

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Cardiology PROCEDURES, LABS, PHYSICAL EXAM ............................................ 5-1

PERIPHERAL AR TERIAL DISEASE ........................................... 5-26 CAUSES OF PAD AND INTERMI T TENT

CHEST X-RAYS ..................................................................................... 5-1 ECH0 ............................... . . ....... . . . . . . ............ . . . .............. . . . ........... . . . . . . . . ...... 5-2

CLAUDICATION .................................................................... 5-26

CARDIAC STRESS TESTS . . . .................... . . . . .............. t......................... 5-2

DIAGNOSIS OF PAD ................................................................. 5-26

Exercise Tolerance Test (Without Imaging) ....................................... 5-2

TREATMENT OF PAD .............................................................. 5-26

Stress Imaging Tests ............................................................................ 5-3

VASOSPASTIC DISEASE .............................................................. 5-27

Cardiac Stress Tests- Picking the Correct Test ................ ,.............. 5-4

CARO TID ARTERY DISEASE ...................................................... 5-27

CARDIOPULMONARY EXERCISE TESTING ..................................5-5

CAROTID ARTERY ATHEROSCLEROSIS............................. 5-27

CARDIAC SCANS I CATHS ............................................... ,................. 5-5

INTERNAL CAROTID ARTERY DISSECTION ..................... 5-28

Contrast Cardiac Catheterization ........................................................ 5-5

CEREBRAL EMBOLIC DISEASE ................................................ 5-28

Cardiac C T ............................................................................. , ............ 5-5

TRANSIEN T ISCHEMIC AT TACK .......................................... 5-28

Cardiac MRJ ........................................................................................ 5-6

AORTIC DISEASE .......................................................................... 5-28

PULMONARY ARTERY CATHETERJZATION .................................. 5-6

AORTIC ANEURYSMS ............................................................. 5-28

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CARDIAC BIOPSY ................................................................................ 5-6

Thoracic Aortic Aneurysms .................................................... 5-28

PHYSICAL EXAM ................................................................................. 5-7

Abdominal Aortic Aneurysm .................................................5-29

Pulses ................................................................................................... 5-7

COARC TATION OF THE AORTA ............................................ 5-29

Heart Sounds and Murmurs ................................................................ 5-7

VALV ULAR HEART DISEASE ..................................................... 5-29

Venous Waveforms.............................................................................. 5-9

INFEC TIVE ENDOCARDITIS ................................................. 5-29

HYPERTENSION ...................................................................................... 5-1 0

Overview .................................................................................5-29

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Antibiotic Prophylaxis ............................................................ 5-30

CARDIAC MEDICATIONS ..................................................................... 5-10

RUBELLA ................................................................................... 5-31

CARDIAC ISCHEMIA............................................................................. 5-IO

RHEUMATIC FEVER ................................................................ 5-31

ANTI-ANGINAL DRUGS ................................................................... 5-12

SPECIFIC VALV E LESIONS ..................................................... 5-3 I

EVALUATION OF CHRONIC STABLE ANGINA ........................... 5-12

Aortic Stenosis ........................................................................ 5-31

Note ...................................................................................................5-12

Chronic Aortic Regurgitation.................................................. 5-32

I. History and Physical Exam: Determine Probabiliry of CAD ...... 5-13

Acute Aortic Regurgitation ..................................................... 5-33

2. Noninvasive Tests for Chronic Stable Angina: Diagnosis and Risk Stratification................................................... 5-13

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3. Determination of Further Workup in Chronic Stable Angina ...... 5-13 TREATMENT OF CHRONIC STABLE ANGINA ............................. 5-14 CARDIOVASCULAR DISEASE (CVD) PREVEN TION

IN WOMEN ........................................................................................ 5-14

ACUTE CORONARY SYNDROME ....................................................... 5-14

CLASSIFICATION OF ACS ................................................................ 5-14

Mitral Stenosis ........................................................................ 5-33 Chronic Mitral Regurgitation.................................................. 5-36 Mitral Valve Prolapse .............................................................. 5-36

Acute Mitral Regurgitation ..................................................... 5-36 Tricuspid Stenosis ................................................................... 5-37

Tricuspid Regurgitation .......................................................... 5-37

Pulmonic Stenosis ................................................................... 5-37

NOTES................................................................................................... 5-15

Pulmonic Regurgitation .......................................................... 5-37

MARKERS FOR AMI .......................................................................... 5-15

Ebstein Anomaly ..................................................................... 5-37

TREATMENT OF ACS......................................................................... 5-16

VALV E SURGERY ..................................................................... 5-37

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Prehospital Management... ................................................................ 5-16

Final Pearls about Murmurs.................................................... 5-38

Evaluation of Patients with Symptoms Suggestive of ACS............. 5-17

ARRHYTHMIAS ............................................................................ 5-38

ACS: GENERAL MEASURES ............................................................ 5-18

MECHANISMS OF ARRHYTHMIAS ..................................... 5-38

ECG, N TG, Morphine, Beta-Blockers, ACE Is, Atropine ................ 5-18

SICK SINUS SYNDROME ........................................................ 5-38

Anticoagulant I Antiplatelet Therapy in ACS ................................... 5-18

HEART BLOCK .......................................................................... 5-38

Fibrinolytic Therapy in ACS............................................................. 5-19

SUPRAV EN TRICULAR TACHYCARDIAS............................ 5-39

Antiarrhythmic Drugs in ACS .......................................................... 5-19

Atrial Flutter ............................................................................ 5-39

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ACS: MANAGEMENT OF UA I NSTEMI-

THE ACUTE ISCHEMIA PATHWAY .............................................. 5-19

Atrial Fibrillation .................................................................... 5-39 MAT......................................................................................... 5-42

Early Invasive vs. Conservative Therapy ......................................... 5-19

SV T.......................................................................................... 5-42

Early Invasive Therapy in UA I NSTEMI ........................................ 5-19

WPW ....................................................................................... 5-42

Early Conservative Therapy in UA I NSTEMI ................................ 5-20

V EN TRICULAR ARRHYTHMIAS .......................................... 5-43

Long- Term Antiplatelet Therapy after UA I NSTEMI..................... 5-20

PVCs ........................................................................................ 5-43

Cocaine and Methamphetamine Users with ST Elevation .............. 5-20 ACS: MANAGEMENT W I TH STEMI OR

Ventricular Tachycardia .......................................................... 5-43 Nonsustained Ventricular Tachycardia ................................... 5-44

NEW LEF T BUNDLE-BRANCH BLOCK ...................................... 5-20

PACEMAKERS........................................................................... 5-44

Note ................................................................................................... 5-20

AN TIARRHYTHMIC THERAPY............................................. 5-45

Immediate Reperfusion Therapies....................................................5-20

Drugs ....................................................................................... 5-45

Additional Recommendations from the 2013

Electrophysiologic Testing ...................................................... 5-46

ACC I AHA STEMI Guidelines .................................................... 5-22

Radiofrequency Ablation ........................................................ 5-46

Complications of Myocardial infarction .......................................... 5-22

SYNCOPE ........................................................................................ 5-47

Implantable Cardioverter-Defibrillators ........................................... 5-23

CARDIOMYOPATHIES ................................................................. 5-48

CORONARY ARTERY DISEASE ........................................................... 5-24

HYPERTROPHIC CARDIOMYOPATHY ................................ 5-48

RISK FACTORS FOR CAD ................................................................. 5-24

Treatment for HCM ................................................................ 5-48

SCREENING ......................................................................................... 5-24

RES TRICTIV E CARDIOMYOPATHY..................................... 5-48

REVASCULARIZATION ..................................................................... 5-24

DILATED AND NONISCHEMIC CARDIOMYOPATHIES ... 5-49

CABG

VS.

PCI ...................................................................................5-24

Stents ................................................................................................. 5-25 Other .................................................................................................. 5-25

The Electrocardiogram HEART FAILURE OVERVIEW

....

...... . . . . ........... . . ...

...

............ . . . . . . . . . .

LOW-OUTPUT HF

.. . . . . . . . .

NYHA Classification ACC I AHA Staging

. .

.....................

....... ............

...

.......

.........

. .

5-49

THE I2-LEAD ECG

5-49

AXIS DEVIATIONS

... ..................

.......... ............

... ........ . . . . . . . . .... . . . .

................. . ........ . . . . . . . . . . . .....

. . . . . . . . . ....... . . . . . . . . ..

. .... .. ..

....

Determining Prognosis in HF ... .

........

. .

. ....................... ..

Mechanism of HF

. .. .. .

....

. . . . ..............

....

.. .

R ATES AND INTERVALS

5-50

INTERVALS

QRS DURATION

.................

PULMONARY EDEMA .. ..

.......

. . . . . .......... . . . . . . . . . . . . . . . . . . . . . . .

....

. . . . ........ . . . . . . . ...

NON-CONSTRICTIVE PERICARDITIS CONSTRICTIVE PERICARDITIS RECURRENT PERICARDITIS PERICARDIAL EFFUSION ASD

5-54

P WAVE

5-54

T WAVE

Ostium Primum ASD Sinus Venosus ASD

...

. . . ..

.....

...

.....

.. .

. . . . . . . ...........

...........

. . . . . . . . . . . . . . . . . . .. . . .

............ . . . . . . . . . . . . . ...................... .........................

PULMONARY STENOSIS

..........................................

... . . . . . . . . . . . . .. . . . . . . . . . . . . .

5-55

LVH

5-56

RVH

.........

ANOMALOUS CORONARY ARTERY

........

.........

......... .................

...............

PULMONARY HEART DISEASE COPD AND S LEEP AP NEA.

. . ....... . . . . . . .....

.....

EISENMENGER SYND R OME

.................

.........

CHRONIC THROMBOEMBOLIC OBSTRUCTION.. PULMONARY ARTERIAL HYPERTENSION P REGNANCY AND THE HEART.. ........ .

...

5-58

. . . . ....

5-59

........................

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5-59

.....

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. ..

...............

...

NOTES

.... . . .

...

. . ...... . . . . ...........

. 5-65

. . . . . . .......

..........................

...

...............

... . . . . . .......

.............................

. . .. .

ANALYSIS

. . . . . . . . . . ............... . . . . . . . .......... . . . . . . . . ...

....

..................................

...................... . . . . . . ......... . . . . . . ..

. . . ..............................................................................

.... . . . . . . . . . . . . . . . . . . ...........

FOR FURTHER READING

5-64

.. 5-65

............

. 5-65

.. .

....................... ...

5-64

.. ..

................

...

. . . . . . . . . . . .......... . . . . . . . . . .....

5-64

. . 5-64

............

.................... ................................. . . .

.......... . . . . . . . . . . ..........

5-63

. 5-63

....................................................

LOCATION OF Ml vs. ECG CHANGES

REMEMBER

5-62

5-64

... . . . . . . . .....

........ . . . . . .. . . . . . . . . . . . . ..... . . .... . . . . . . . . . . . . . . ........

COMMON FINDINGS

.5-58 5-58

.. ......... . . ...... .

......

....

.... .........

......................................... .............

MYOCARDIAL INFARCTION

5-58

..........................

..........

VENT RICULAR ECTOPIC BEATS AND HEART BLOCK

5-58

...............

.............. . . . . . .........

..................................

5-62

...............................................

.....

.................. . . .

ATRIAL ARRHYTHMIAS

5-58

........

...............................................................

ECTOPIC vs. PACEMAKER

5-58

.......

...................................................... . . . . ...........

WIDEQRS

..... . . . . . . . . . .....

....

ARRHYTHMIAS

5-58

SUDDEN DEATH IN EXERCISING YOUNG PEOPLE OTHER

LPFB

. . . . . . . . . . . . . . . . . . . . ......

......

5-6I

...... . . . . . . . . . . . . . . .......................... .... . . . ................ . . . . ........... . .

Bifascicular Block

5-57

.........

................

RBBB

5-58

......

5-6 I

. .. 5-63

............... ..

......... ...... ..................................................

LAFB.

. . ........

V d ti e n U LBBB

5-57

..................

BUND LE-BRANCH BLOCK

. . .....................................................................

COARCTATION OF THE AORTA

G R .

....

......................................................................

5-57

. 5-57

.................

........

..............................................................................................

AV BLOCKS

5-57

...

.................... . . . . . ...................... . . . . . . . ............ . . . . . ..

CONDUCTION DISTURBANCES

..........

. . . . . . . . . . . . . . . ............. . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . ................. .........

5-57

.....

. . . . . . . ................................................................................

VENTRICULAR HYPERTROPHY

5-55

. 5-57

..............

5-6I

S T SEGMENT ............................................................................. 5-62

....................... . . . . . . .

. . . .. . . .

................. . . .

QRS COMPLEX

..............................

...

5-6 I 5-6I

5-55

5-56

. .

................................................

. . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . ..................... .........

5-60

5-55

............................................

................

... . . . . .

U WAVE....................................................................................... 5-62

.......................................................... . . . . . . . . . . . . . . . . . ...................

VSD

................ . . . . . . . . . . . . . . . . . . . . . . ......

. . . . . . ...

Ostium Secundum ASD . .

PDA

................. . . . . . . . . . .......

....... . . . . . . . . ...

CONGENITAL HEART DISEASE

.........

................... ...............

....................................................

5-60

WAVEFORMS AND SEGMENTS ................................................. 5-6 I

RIGHT VENT RICULAR FAILURÂ£.. ........................................5-54 PERICARDIAL DISEASES

... . . . . . . .

............................................................................

QT INTERVAL

..................

.. .. ...

.... . . . . . ......

5-51

..................... . . . . . . . . . . . . . .

................................. . . . . . . . . ....

. . . . . . . . ................................................ ................

5-51

...... . . . . . . . . . . .

Emergency Treatment for Severe Heart Failure . .. ............... . . . ....

....... . . . .

P R INTERVAL

5-50

....

Treatment for HF..................................................................... 5-52 HIGH-OUT PUT HF .

5-50

. . . . ...............

...................

5-60

.................................................... . . . . . . .......... . . . .

.............

................................ . . . . ............ . . . .

............................................................

5-65 5-65 5-65 5-66 5-66 5-66 5-66 5-66 5-67 5-67 5-67 5-81

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PROCEDURES, LABS, PHYSICAL EXAM

upper lobe pulmonary veins), Kerley B lines, and pleural

PROCEDURES, LABS, PHYSICAL EXAM

effusions (usually right> left). An anomalous pulmonary vein that drains into the

CHEST X-RAYS

inferior vena cava can create a "scimitar sign" on chest

Know all the following chest x-ray findings!

x-ray. This is a curvilinear opacity in the right lower

Chest x-ray is an effective means of quickly determining significant increases in both overall heart size and (sometimes) heart chamber sizes. A cardiothoracic ratio >

50% indicates an enlarged cardiac silhouette, sug

gesting either cardiomegaly or a pericardia! effusion. This is the ratio comparing the most rightward and

lung field due to associated lung hypoplasia. Aortic abnormalities that you may see include tortuosity

and calcification. An aortic aneurysm is sometimes easily visible on the lateral film. An aortic dissection can show up as mediastinal widening on the PA projection.

leftward borders of the heart seen on a posteroanterior

Pericardia! effusion is suggested by a "water bottle" or

(PA) chest x-ray, divided by the transverse chest diam

a "water balloon" shape to the heart, sometimes with sig

eter (measured from the inside rib margin at the widest

nificant enlargement of the cardiac silhouette (Image 5-3).

point above the costophrenic angles on the same x-ray). This ratio is valid only for an upright, nonrotated film on full inspiration (diaphragm fully contracted) with a well-visualized cardiac outline and when there is no abdominal compression on the diaphragm, such as that caused by ascites or pregnancy. On the PA film, the left ventricle causes the bulge in the left-lower side of the cardiac shadow; the right atrium

(RA)

causes the outline on the right; and the area of the

cardiac "waistline"-between the aortic knob and the left ventricle (LV)-is formed by the main pulmonary artery and the left atrial (LA) appendage (Image

5-1).

On the lateral view, any increase in the mass of the left ventricle extends the cardiac shadow posteriorly and lower-closer to the diaphragm. Any increase in the mass of the right ventricle fills in the lower part of the anterior clear space behind the sternum (Image

5-2).

Coarctation of the aorta (COA) is indicated by absence

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of a normal aortic arch. Instead, look for the

"3" sign,

which is created by a prominent, left subclavian artery,

visible

with

significant

left-to-right shunts.

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Areas of calcifications on chest x-ray: •

Aortic: Think dissection if you see a separation between calcification and the aortic border, especially

if the mediastinum appears wide.

•

Myocardial: typically from an apical aneurysm.

•

Valvular: commonly aortic.

•

Annular (ring-shaped): mitral annular calcification; if it is a perfect ring then a prosthetic valve is likely (especially if surgical clips are also present).

•

P ericardia!: Think constrictive pericarditis; or think TB if the clinical history suggests significant

exposure (Image

5-4).

3,"

due to the impressions of the arterial structures on the esophagus. Adults also show intercostal rib notching due

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to collateral flow through tortuous intercostal arteries. Heart

failure

(HF) is indicated by cardiomegaly,

pulmonary vascular redistribution (with visibly thickened

Image 5-1: Normal posteroanterior chest x-ray

MedStudy

ventricular

septal defect (VSD), atrial septal defect (ASD), or other

the coarctation, and poststenotic dilation of the descend ing aorta. The barium swallow can show a "reversed

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Shunt vascularity (enlarged, sharply defined pulmonary vasculature)

Image 5-2: Norma/lateral chest x-ray

5-1

5-2

PROCEDURES, LABS, PHYSICAL EXAM

intracardiac shunts. Doppler echocardiography measures the velocity and direction of the blood flow. Doppler echo determines mean gradients, peak velocities, and valve area. So, Doppler is useful in determining the severity of valvular stenosis or regurgitation, as well as in evalu ating left ventricular diastolic function, left ventricular outflow tract gradients, and intracardiac shunts. It is also helpful in estimating pulmonary artery (PA) pressure. To estimate pressure by using peak Doppler velocity

Image 5-3: "Water bottle" heart

measured on echo: P ressure gradient (mmHg) = 4 x V2

Image 5-4: Pericardia/ calcification

(measured velocity). For example, if the velocity across the tricuspid valve is

Know that a single lead in the apex of the right ventricle (RV) indicates the presence of an electronic ventricu lar pacemaker or implanted

defibrillator-with the

5 m/sec, then the PA pressure =

4 x ( 5 x 5) + right atrial pressure. So, if the right atrial

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pressure in this example is

defibrillator lead being larger and wider than that of a pacemaker, 2 leads indicate an atrioventricular (AV ) sequential

(dual-chamber)

pacemaker,

and

leads

10 mmHg, then the PA

pressure= 110 mmHg (which is extremely high).

CARDIAC STRESS TESTS

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indicate a biventricular pacemaker. If there is no atrial

Overview

lead, the patient likely has chronic atrial fibrillation.

The increased demand for myocardial oxygen with exercise is the key factor in the use of exercise testing as a diagnostic tool for coronary artery disease ([CAD];

ECHO Echocardiography is an ultrasound modality used to

a.k.a. coronary heart disease). Stress tests have an integral role in both the detection of CAD (diagnostic tool) and

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image the heart. It utilizes M-mode, 2D, and 3D for

in stratification of risk (prognostic tool). To appropriately

structural imaging and Doppler for assessing blood flow

utilize stress tests, a patient's pretest probability of CAD

rate and direction.

must be taken into account. (A positive test in a low-risk

Best use of echo is for the following scenarios: •

Left ventricular structure and systolic function

•

Right ventricular structure and systolic function

•

Valvular heart disease

•

Congenital heart disease

•

Myocardial infarction (including post-MI

•

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complications)

patient is more likely to be a false positive, and a negative test in a high-risk patient is more likely to be a false nega

tive.) Diagnostic testing is most valuable when pretest probability for CAD is intermediate.

There are 2 general types of cardiac stress tests done:

I) Exercise tolerance test ([ETT]; basic treadmill or stationary bicycle testing without imaging)

2) Stress imaging testing-"stress" is induced with:

Cardiomyopathy (both loss of ejection fraction and hypertrophy of myocardium)

•

Pericardia! disease

•

Cardiac masses (tumor, thrombus, and vegetation)

•

exercise (treadmi11 or bicycle), or

•

pharmacologic stress (either dobutamine or a vasodilator)

The associated imaging is done with:

•

Diseases of the aorta and pulmonary artery

•

Estimation of pulmonary pressure

•

Echocardiography (a.k.a. "stress echo")

•

Diastolic function

•

Myocardial perfusion imaging (MPI)

•

Cardiac sources of emboli

Transesophageal echocardiogram (TEE) is an echo performed

with

higher-resolution

esophageal

images

compared

probe. to

offers

transthoracic

Left atrium (including left atrial appendage)

•

Cardiac masses

•

Intracardiac shunts

•

Endocarditis

•

Aortic dissection

or stationary bicycle, is the cornerstone of diagnostic determining prognosis (including post-MI).

Valvular structure and function

•

Exercise tolerance test (ETT), using either a treadmill testing for ischemia and functional capacity and for

imaging and is especially useful for evaluating: •

Exercise Tolerance Test (Without Imaging)

Despite an overall low sensitivity and specificity (men: sensitivity= 68%, specificity= 77%; women: sensitivity =

61%, specificity = 70%), the sensitivity and specific

ity increase with higher pretest probability of CAD. ETT has a number of advantages, including: the ability to test functional capacity, safety, widespread availability, and

A bubble study (performed by injecting hand-agitated

relatively low cost.

saline and air into the venous system) is used to evaluate

PROCEDURES, LABS, PHYSICAL EXAM

•

Q�uiz •

On a lateral view

•

CXR,

extension of the heart

enlargement of which ventricle? On a lateral view

CXR,

extension of the

cardiac shadow of the lower part of the anterior clear space behind the sternum indicates

What conditions is a TEE useful for evaluating?

•

What are absolute indications for terminating

Absolute contraindications to ETT:

an ETT? •

•

When are stress imaging studies done instead of an ETT?

•

The patient typically exercises on a treadmill using standard exercise protocols, such as the Bruce protocol (see Table 5-6 on page 5-12). The level of maximal exercise achieved on the ETT is measured in metabolic equivalents (METS). ETT should not be performed in 2 groups:

I) Patients unable to exercise sufficiently (must achieve 85% of age-predicted maximum heart rate) 2) Patients with baseline ECG abnormalities that can interfere with interpretation of the stress test (e.g., left ventricular hypertrophy [LYH], left bundle-branch block [LBBB], Wolff-Parkinson-White [WPW], ventricular pacing, and resting ST depression), or taking digoxin

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Know the following information related to ETTs:

Definition of a positive ETT: flat or down-sloping ST-segment depression > I mm and 80 ms after the J-point in 3 consecutive beats.

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Unlike ST elevation, ST depression does not correlate with the anatomic location of myocardial ischemia. Isolated ST depression in inferior leads is far less specific than ST depression in lateral leads (V4-V6).

ST elevation during an ETT in 3 contiguous leads without Q waves of prior MI is an unusual finding that is suggestive of marked ischemia (can be seen also with coronary artery spasm). Absolute indications for termination of an ETT: •

•

ST elevation > I mm in leads without Q waves from prior MI and excluding aVR, aYL, and VI Decrease in systolic BP > I 0 mmHg when accompanied by any other evidence of ischemia or hypoperfusion

•

Moderate-to-severe angina

•

CNS symptoms (ataxia, dizziness, near syncope)

•

Signs of poor perfusion (cyanosis/pallor) Sustained 2nd or 3rd degree AV block

Serious arrhythmia (e.g., sustained ventricular tachycardia)

Excellent exercise tolerance (> I 0 METS) is associated with a good prognosis independent of the degree of coronary artery disease.

enlargement of which ventricle? •

Patient requests to stop

Achieving target heart rate alone is not a reason to discontinue the ETT, and the individual should be encouraged to go as long as tolerated until required to stop for some reason (e.g., dyspnea, fatigue, exhaustion, or one of the absolute indications for termination).

border posteriorly and inferiorly indicates

•

Technical difficulties in monitoring ECG/BP

G R

Acute MI within 2 days

Unstable angina not previously stabilized by medical therapy

Uncontrolled arrhythmias causing symptoms or hemodynamic compromise

V d ti e n U •

•

Symptomatic severe aortic stenosis

Uncontrolled symptomatic heart failure

Acute pulmonary embolus or infarction

•

Acute myocarditis or pericarditis

•

Acute aortic dissection

Stress Imaging Tests

Overview

The stress imaging studies are the stress echo and myocardial perfusion imaging (MPI). The choice of which one to use is often based on operator experience at the facility. Stress imaging studies are used as the initial diagnostic method when a patient is not a candidate for ETT due to inability to exercise adequately or when there are ECG changes at rest that can interfere with interpretation of the ETT. They also are preferred in patients with prior revascularization.

Stress imaging studies have greater sensitivity and specificity than the regular ETT. They are used when measurement of ejection fraction or myocardial viability is desired in addition to identifying coronary artery disease.

Stressing the Heart for Imaging Studies The "stress" portion of these tests can be performed with exercise or pharmacologic agents. With exercise, imaging studies are done just like an ETT and require the same ability to meet 85% of age predicted maximum heart rate. Exercise is preferable because it provides additional functional and prognostic information. Exercise is not used in patients with pace makers or left bundle-branch block (LBBB) because it can cause false-positive left ventricular anteroseptal perfusion defects. The pharmacologic agents used for cardiac imaging studies are dobutamine or vasodilators.

5-3

5-4

PROCEDURES, LABS, PHYSICAL EXAM

Dobutamine is both inotropic+ chronotropic and causes

dilation and decline in global left ventricular systolic

the heart to act similarly as it would with exercise. As

function with stress (suggestive of multivessel disease).

with exercise, a target heart rate must be achieved with

Stress echo is less expensive than MPI.

dobutamine. Also, as with exercise, dobutamine is not used in patients with pacemakers. Dobutamine stress echo is fine for LBBB (but not dobutamine MPI with LBBB). Dobutamine is the agent used for patients who not only are unable to exercise but who also have a con traindication to vasodilators (e.g., bronchospasm, severe

Vasodilators are not used for stress echo. Myocardial P erfusion Imaging

Myocardial perfusion imaging (MPI) uses radioisotopes with

single-photon

emission computed

tomography

carotid artery stenosis).

(SPECT).

Vasodilation: Adenosine,

technetium-99m (99mTc)-labeled substances (commonly

dipyridamole, and regad

enoson are the main coronary vasodilators used in the

The

most

commonly

used

agents

are

sestamibi or tetrofosmin). Thallium-201 (2°1TI) is Jess

pharmacologic MPI stress tests. Vasodilators do not

commonly used.

stress the heart by increasing heart rate as is done with

These tracers distribute in heart tissue in proportion to

exercise or dobutamine. These vasodilators work in this setting by dilating and increasing blood flow in normal cardiac vessels while doing little to change the flow in stenotic vessels. The dilated normal vessels steal flow from the stenotic vessels, causing perfusion defects in scans (and ST segment changes in ECGs). Vasodilators are not used in patients with history of bronchospasm. Regadenoson is a more selective A2A receptor activator, has less bronchospasm effect, and allows for a faster stress test. Even so, for the Boards and per current

blood flow; this distribution is recorded by a gamma camera. Perfusion is compared visually between the resting and stressed states. Preserved myocardial perfu sion at rest but decreased during stress is suggestive of ischemia ("reversible defect"), while matched reduction in perfusion between the rest and stress images is sug gestive of a myocardial infarction ("fixed defect"). Other high-risk markers include transient ischemic LV dilation (TID), reduced post-stress LV ejection fraction, and increased lung or right ventricular uptake, all of which

guidelines, dobutamine is still the pharmacologic agent

are suggestive of multivessel disease.

of choice for patients with a history of bronchospasm.

MPI is often done with ECG-synchronized "gated"

Stress Echo and Stress MPIIndications

smoothed for better resolution. This allows for assess

technique, where multiple images are combined and

Unlike ETT, exercise stress echo and stress MPI can be used in patients: •

•

ment of wall motion and ventricular size and function (estimates ejection fraction). Again, target heart rate must be achieved with exercise

with resting ECG ST changes,

or dobutamine for an adequate test; however, achieve

with WPW syndrome, or

ment of target heart rate is not needed with vasodilator

on digoxin therapy.

stress. So, dobutamine is used only in cases where the

Note that it is a common misconception that these patients require chemical stress, but this is definitely not true! If

vasodilator is contraindicated (as it would be in patients with bronchospasm-see above).

they can exercise, these patients have a class I indication

Other imaging modalities that can be used for MPI

for a stress echo with exercise or MPI with exercise (i.e.,

(other than SPECT imaging) include cardiac positron

these patients need the imaging, not the chemical stress). Note: MPI with vasodilators (but not exercise or dobu tamine!) is the test of choice for patients with paced ventricular rhythm.

emission tomography (PET) and cardiac MRl, both of which are also used to assess for myocardial ischemia and viability. Myocardial perfusion imaging (MPI) is more expensive than stress echo, and it involves radiation exposure.

Stress Echo

The stress echo is a widely used test for myocardial

Cardiac Stress Tests -

ischemia by the detection of stress-induced wall motion

Picking the Correct Test

abnormalities. Stress echo is less sensitive but more spe

To determine the correct stress test, go through the

cific than MPI for the detection of coronary artery disease. Use exercise or, if unable to exercise, use dobutamine to achieve target heart rate. Then take echo images to evaluate changes in wall motion, systolic wall thickening, and sys tolic ejection fraction with stress. Abnormal wall motion or failure of the wall to thicken (contract) appropriately sug gests ischemia of that region of the myocardium.

following scenarios. These are summarized in Table 5-1. An exercise stress test (i.e., ETT, exercise echo, exercise MPI) is always preferred if the patient has no limitations to exercise (exceptions are LBBB or paced rhythm). If the resting ECG is normal, proceed with ETT no imaging is needed. If the resting ECG is abnormal (with exception of LBBB and paced rhythm), perform

In addition to new regional wall motion abnormalities,

exercise testing with echo or MPI.

criteria for abnormal stress echo are left ventricular cavity

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

PROCEDURES, LABS, PHYSICAL EXAM

response to intervention. CPX is well established for evaluating patients with systolic heart failure

(HF),

undergoing a pretransplant assessment, and for patients with unexplained exertional dyspnea. When are exercise stress echo and MPI

•

indicated instead of ETT?

CARDIAC SCANS I CATHS

Which stress imaging tests are used in patients

•

Contrast Cardiac Catheterization

with LBBB? With paced ventricular rhythm?

Coronary

Which patients may benefit from CPX?

•

the

A pharmacologic stress test is done if the patient cannot do more than moderate exercise, is unable to increase the heart rate (e.g., pacemaker) or has LBBB. Follow these indications when choosing the proper agent:

angiography

diagnosis

coronary

the

gold

artery

standard

disease

for

(CAD);

ventriculograms and aortic root angiography can be done at the same time as the coronary angiogram. Not only can contrast cardiac catheterization assess coronary anatomy through contrast ventriculography, it also can assess ejection fraction, wall motion abnormali

•

If the patient simply is unable to walk and has no

ties, ventricular dilatation, degree of mitral regurgitation,

other issues, use pharmacologic stress test.

and the presence of a ventricular aneurysm. Cardiac

•

If the patient has bronchospasm or severe carotid

catheterization is an invasive procedure with

artery stenosis, use dobutamine.

of serious complications (death, M I, stroke, arrhythmia,

If the patient has severe HTN or prior ventricular

renal failure, bleeding).

•

tachycardia (VT), use a vasodilator (adenosine,

I% risk

These studies all involve arterial access, radiation, and

dipyridamole, or regadenoson), not dobutamine. •

contrast exposure.

If the patient has a paced ventricular rhythm, use a

Cardiac CT

vasodilator with MPI; again, not dobutamine. One more time: Do not use adenosine or dipyridamole

Cardiac CT is a newer, noninvasive modality for imaging

in someone with asthma or severe carotid stenosis and

the heart. Cardiac CT includes:

do not use dobutamine in someone with a history of VT, uncontrolled HTN, or a paced ventricular rhythm.

•

Coronary computed tomographic angiography (CTA)

•

Coronary artery calcium (CAC) scoring

•

Assessment of ventricular structure and systolic

CARDIOPULMONARY EXERCISE TESTING Cardiopulmonary

exercise

testing

special exercise test that measures

(CPX)

ventilation and

concentrations of oxygen and carbon dioxide during progressive exercise (stationary bicycle/treadmill) and is the gold standard aerobic exercise test. CPX provides the most accurate and reproducible measurement of cardiorespiratory fitness, severity of impairment, and

function

CTA requires IV contrast (check Cr!); also, the heart rate must be < 60 bpm and regular, and patients must be able to hold their breath. CTA is a reasonable diagnostic test for symptomatic patients who are at intermediate risk for CAD after initial risk stratification, including patients with equivocal stress

Table 5-1: Determining Best Cardiac Stress Test ECG Findings

Able to Exercise? Able

Resting ECG

ETT*

normal

NotAble

depression, WPW,

LBBB

Pacemaker

reduced in patients with pronounced coronary

Exercise MPI*

Dobutamine MPI Vasodilator MPI

N/A

CTA is an excellent test for evaluation of patients with congenital coronary anomalies.

CAC (coronary artery calcium) scanning detects atherosclerosis

and,

unlike

CTA,

does

not

Vasodilator MPI*

require IV contrast. CAC is used for further risk

Dobutamine echo

stratification in asymptomatic, intermediate-risk

Vasodilator MPI

preferred. Vasodilators= adenosine, dipyridamole, regadenoson. Vasodilator used if patient has previous V-tach or severe HTN. Vasodilator not used if patient has asthma or severe carotid stenosis; instead, use dobutamine. *

negative CTA is very helpful in excluding sig nificant coronary artery disease. Usefulness is calcification.

Dobutamine echo

N/A

predictive value of CTA is very high; that is, a

Dobutamine echo

Exercise echo*

LVH, digoxin

atic patients or in symptomatic patients with very low or high probability for CAD. The negative

Dobutamine MPI Vasodilator MPT

> I mm resting ST

test results. It should not be used in asymptom

patients. A CAC score of zero is considered low > 400 indicates an elevated 3-fold) risk for CAD.

risk for CAD, and (

5-5

5-6

PROCEDURES, LABS, PHYSICAL EXAM

A noncontrasted chest CT (which differs from a dedicated cardiac CT) is highly effective in assessing for pericardia! thickening if constriction is a concern. Keep in mind that all forms of cardiac CT involve radiation exposure. Cardiac MRI

Static and dynamic cardiac MRI (CMRI) allows high resolution imaging of ventricular function, valvular motion, and myocardial perfusion. CMRI is useful to assess cardiac structure and function, valvular heart disease, coronary takeoff, the great vessels, pericardia! disease, cardiac masses, myocarditis, and infiltrative diseases. CMRI also can be used to assess for myocardial ischemia and post-MI tissue viability. Cardiac MRI involves the use of gadolinium, which should be avoided in patients with advanced renal failure due to the risk of nephrogenic systemic fibrosis. PULMONARY ARTERY CATHE TERIZATION

Pulmonary artery catheterization (PAC) can be used to assess right and left filling pressures, cardiac output, RV and PA pressures, and systemic and pulmonary vascular resistance. This is useful to determine a patient's volume status, causes of shock, and existence of pericardia! disease. The pulmonary capillary wedge pressure (PCWP) is the dampened L A pressure that reflects left ventricular end-diastolic pressure (LVEDP) in most cases. This reflects LVED volume. Know this entire topic! Normal pressures (mmHg): •

•

RA < 7, RV 30/7, PCWP < 12. Jugular venous distension in the upright patient indi cates an elevated R A pressure> 7 em H20 (5 mmHg). PCWP increases with LV systolic and diastolic failure, mitral stenosis, aortic and mitral insufficiency, tampo nade, and constrictive pericarditis. Consider LV failure if the PCWP is> 15-18; PCWP 15-25 causes dyspnea on exertion (DOE); and PCWP 25-35 causes dyspnea at rest, orthopnea, and interstitial edema. Pressure> 35 (acutely) causes frank pulmonary edema. =

for the tests that differentiate between these disorders (page 5-55). 3) If the cardiac output and PCWP are decreased and the RA pressure is elevated in the setting of an acute inferior Ml, the cause is RV infarction with secondary right-sided failure. The RV has decompensated and is unable to fill the left side of the heart. Treatment is to give fluid until the blood pressure returns to normal. This sounds like stressing an already stressed RV and it is-but there is a net positive effect when BP and, hence, coronary artery blood flow are returned to normal and heart rate is reduced. Think of this in a hypotensive patient with an inferior infarction and raised jugular venous pressure (JVP). Do not give preload-reducing agents such as nitroglycerin because cardiac output depends on adequate preload in the setting of an RV infarct. 4) If the cardiac output is low, PCWP high, and RA pressure high, the patient has biventricular failure with cardiogenic shock. Treatment is to give diuretics, preload and afterload reducers, and inotropes. In a typical case, a patient gets nitroprusside, nitroglycerin, milrinone, or dobutamine. 5) Mitral stenosis (or LV failure) with 2° RV failure. 6) Pulmonary hypertension. Also know that septic shock is mainly due to a low systemic vascular resistance. These patients have low BP, systemic vascular resistance (SVR), and PCWP and a high CO. CARDIAC BIOPSY

Endomyocardial biopsy is used to evaluate the cause of a cardiomyopathy or myocarditis in patients where the diagnosis is uncertain and would change management, or if the patient is not responding to therapy. Monitoring cardiac transplant rejection is the major indication for endomyocardial biopsy. It also can be considered in patients with rapidly progressive heart failure or wors ening ventricular dysfunction that persists despite appropriate medical therapy, and in patients suspected of having myocarditis (particularly giant cell myocar ditis) or a myocardial infiltrative process (particularly amyloidosis). Table 5-2: Pulmonary Artery Catheterization Scenanos

Note: The RA pressure and PCWP also increase with decreased compliance of the ventricle (as in LVH and right ventricular hypertrophy [RVH]). A few PAC scenarios are shown in Table 5-2:

PA Press

PCWP

0--5

(13-28)/ (3-13)

3-11

110/70

32/18

70/50

21/11

70/50

30/20

70/50

90/32

110/70

90/32

110/70

Press (normal)

1) Normal: Notice in the examples that the diastolic PA pressure is typically very close to PCWP (usual difference < 5) except in #6, in which there is pulmonary hypertension! 2) Diastolic pressure in all 4 chambers is equalized in both pericardia! tamponade and constrictive pericarditis. See the Pericardia! Diseases discussion

PROCEDURES. LABS, PHYSICAL EXAM

Pulsus

parvus

tardus

tardus-slow upswing)

(parvus-low

amplitude,

aortic stenosis.

B rachiofemoral delay, the femoral pulse occurring after the brachial pulse, is present in coarctation of the aorta.

•

When is PCWP increased?

•

When is diastolic pressure equal in all

Pulse asymmetry occurs in aortic dissection, with good upper-extremity pulses and diminished or absent lower

4 chambers? •

extremity pulses, or the asymmetry occurs between the left and right extremities.

Name 1 indication for doing endomy ocardial biopsy.

•

Peripheral arterial disease ([PAD]; previously called peripheral vascular disease [PVD]) can cause decreased

True or false? Pulsus paradoxus can be seen in

or absent peripheral pulses; a bruit may be heard over the

cardiac tamponade. •

more proximal artery (such as the femoral artery) as well.

What is pulsus bisferiens? What does it indicate?

•

What does pulsus alternans indicate?

Heart Sounds and Murmurs

•

True or false? Sustained handgrip increases the

Heart sounds and murmurs: Again, know this topic! Know the differentiating maneuvers in Table 5-3 and

murmur of mitral valve prolapse, but decreases

the heart sounds tables in the Valvular Heart Disease dis

the murmur of HCM.

cussion (Table 5-I 0 and Table 5-11 on page 5-34 and

The sensitivity of endomyocardial biopsy in many conditions that affect the heart focally is relatively low, so a "negative" biopsy is not as helpful as a

page 5-35). Learn these topics so you can determine how one abnormal finding (e.g., a particular heart sound) suggests certain findings on ECG and chest x-ray.

"positive" one. Murmurs

All valve murmurs increase in intensity when blood

PHYSICAL EXAM

flow increases across the valve. Standing and the strain

Note

phase of Valsalva decrease right and left cardiac fill

Know this physical exam topic perfectly! You should know normal findings as well! Consider this whole topic highlighted!

passive straight-leg raises if already supine) increase pulse

amplitude with

inspiration seen as absence of Korotkoff sounds during inspiration) can be observed clinically by auscultating the BP and listening for an exaggeration of the normal inspiratory decrease in systolic BP

(> 10 mmHg).

It is present with:

•

Sustained handgrip (20-30 seconds) boosts systemic vascular resistance and left ventricular volume, and therefore decreases the murmurs of HCM and aortic earlier prolapse of the valve; thus, it helps differenti ate between HCM and MVP. Typically, use handgrip

constrictive pericarditis,

to differentiate between AS (murmur decreases) and

asthma, and

MVP (murmur increases in duration).

tension pneumothorax.

Note: Korotkoff sounds are those heard during blood pressure determination with a cuff. heartbeat but not feel a pulse during inspiration. cycle) is seen with aortic regurgitation (with or without stenosis!) and hypertrophic cardiomyopathy (HCM, page 5-48). pulse

during inspiration and any maneuvers that increase

pressure

return,

such

passive

leg

raising

and

abdominal compression. Left-sided murmurs and heart sounds are louder during expiration. The only semi

Pulsus bisferiens (bifid with 2 systolic peaks per cardiac

(varying

Right-sided murmurs and heart sounds are louder venous

The paradox is that, when severe, you can hear a

altemans

also increases intensity of all murmurs except, again, MVP (page 5-36) and and HCM (page 5-48).

stenosis (AS). It prolongs the murmur of MVP due to

cardiac tamponade (especially),

Pulsus

of mitral valve prolapse (MVP) and hypertrophic car

cardiac volume. This increased volume and afterload

Pulsus paradox us (decreased

•

but these actions increase the intensity of the murmurs diomyopathy (HCM). Squatting and lying down (or

Pulses

•

ing and cause the sound of most murmurs to decrease,

with

regular pulse rate) is seen with severely depressed

exception to this rule is a right-sided ejection click due to pulmonic stenosis; this disappears with inspiration. (On a chest x-ray, pulmonic stenosis can appear as an enlarged pulmonary artery.) Heart Sounds

systolic function of any cause that leads to decreased

51 is caused by the closing of the mitral and tricus

stroke volume.

pid valves. S1 intensity is decreased when there is

MedStudy

5-7

5-8

PROCEDURES, LABS, PHYSICAL EXAM

a prolonged PR interval, mitral regurgitation, acute

stenosis, acute pulmonary embolism, ectopic or pace

aortic regurgitation (increased LV pressures cause early

maker beats originating in the left ventricle, or right

valve closure), or with a severely calcified mitral valve.

bundle-branch block (RBBB)-all of which cause

sl intensity is increased (i.e., the mitral valve slams shut) by a short PR interval, mitral stenosis, or hyperdynamic ventricular function. 52 is caused by the closing of the aortic (A2) and pulmonic (P2) valves at the end of systole. P2 usually occurs just after A2; this physiologic split is increased with inspiration, because the increased volume of blood in the right ventricle prolongs RV systole and delays closure of the pulmonic valve. It generally disappears on expiration. A persistently (or widely) split S2 can vary with respiration but does not disappear

on expiration.

A widely split S2 that varies with inspiration (but never completely disappears) can be due to pulmonic

delayed or prolonged contraction of the right ventricle. A widely split S2 can also be caused by early closure of the aortic valve, as in mitral regurgitation. Pulmonic stenosis is especially likely if the patient has an ejec tion click that disappears with inspiration. You hear a fixed split S2 when there is an atrial septal defect. The patient presents with a fixed, split-second heart sound, a systolic ejection murmur (SEM), and has pulmonary vascular congestion on the chest x-ray. You can also hear a fixed split S2 with RV failure when the stroke volume is unable to increase with inspiration. A delay of aortic closure (A2) causes a paradoxically split S2> with P2 occurring before A2. In this case you hear increased splitting with expiration instead of

Table 5-3: Maneuvers to Differentiate Murmurs Maneuver

Result

Passive straight-leg raise (to 45 degrees, listen after 15 sec)

Increases venous return

Valsalva (hold for 20 sec, listen just before end)

Decreases venous return

Standing (squat for> 30 sec then quickly stand; listen during

Decreases venous return

first 15 sec after standing) Transient arterial occlusion (bp cuff on both arms, inflated

Increases systemic vascular resistance

> 20 mm above systolic pressure) Handgrip (isomeric; listen at end of 1 min max grip)

Increases systemic vascular resistance

Squatting

Increases venous return and increases systemic vascular resistance, but preload effect is stronger than afterload effect

Maneuvers for increasing/decreasing specific systolic murmurs For HCM use

Result

Standing (from squat)

95�o get increased murtnur

Valsalva (if cannot do squat-to-stand)

65% get increased murmur

Passive straight-leg raise

85% get decreased murmur

Handgrip

85% get decreased murmur

Result

ForMVP use Standing and Valsalva

Click-murmur moves earlier

Transient arterial occlusion

In 80%, click-murmur moves later

Handgrip

In 70%, click-murmur moves later

Result

For VSD use Standing and Valsalva

Murmur decreased

Transient arterial occlusion

80% get increased murmur

Handgrip

70% get increased murmur

Result

For AS use Transient arterial occlusion

Murmur decreased

Handgrip

Murmur decreased

PROCEDURES, LABS, PHYSICAL EXAM

with concentric hypertrophy. You do not hear an S4 during atrial fibrillation because the sound requires atrial contraction. S4 also is not audible in mitral steno sis, where there is obstruction of the ventricular inflow. •

When is a persistently split S2 heard?

•

What causes a paradoxically split S2?

•

When is an S3 important?

•

When are large

Venous Waveforms Venous

waves seen on the left side?

When is rapid x and y descent seen?

•

When are large, right-sided a waves seen?

•

When are large, left-sided a waves seen?

•

When are "cannon" a waves seen?

•

When does a slow y descent occur?

venous

pressure

and

Large, right-sided

waves are seen in ventricular

septal rupture and tricuspid regurgitation. •

•

Jugular

the neck (Figure 5-l ). [Know these!] See Table 5-4.

Right side? •

waveforms:

waveforms are typically examined on the right side of

With severe mitral regurgitation, there are tall, left-sided

waves from the regurgitation

during systole. Note that left-sided waves are not seen on the NP but on Swan-Ganz monitoring. •

Rapid x andy descents are seen with constrictive pericarditis, whereas only a rapid x descent is seen in

inspiration. This delay is commonly caused by LBBB and ectopic or pacemaker beats originating in the right

tamponade (loss of they descent). •

ventricle. Advanced HCM is another cause. filling

(sounds

waves are seen in tricuspid

stenosis (TS), severe pulmonic stenosis, and severe noncompliant RVH.

53 just follows S2 and indicates the end of rapid

ventricular

Large, right-sided

lub-dub-huh);

this

•

waves are seen with mitral

stenosis (MS).

is the first part of diastole, when the first 70% of ventricular filling occurs as the ventricle relaxes.

Large, left-sided

•

The sound is thought to be due to the tensing of the

"Cannon"

waves occur in complete heart block,

ventricular tachycardia, or asynchronous ventricular

chordae tendineae. You often hear it in normal children

pacing and all conditions withAV dissociation (times

and in persons with high cardiac output, such as preg

when the atrium is contracting against a closed

nant women, but it is typically an abnormal finding in patients

40 years of age. In these patients, it can be

from any condition that increases early LV filling rate or volume, such as acute ventricular decompensation or severe aortic or mitral regurgitation. S3 in a patient with known left ventricular dysfunction is a poor

tricuspid valve). •

Slow y descent is from delayed atrial emptying as in tricuspid stenosis.

Also see Table 5-l 0 on page 5-34 for a review of the valve disorders.

prognostic indicator-in general, as well as for surgery. Both S3 and S4 are best heard in left lateral decubitus position using the bell. a

54 is heard just before S 1 at

the end of diastole (sounds

Ventricular

like huh-lub-dub). The S4 sound is

caused by

Diastole

Systole

ven

tricular filling during atrial contraction, and you hear it in patients with decreased compliance.

ventricular Increased

stiffness

ventricles

causes

ful

atrial

the

force

contraction

and

causes S4. You may hear S4 in ischemic heart disease, aortic stenosis, hypertrophic cardiomyopathy,

dia

betic cardiomyopathy, and hypertensive heart

disease

xdescent

v wave

y descent

Atrium contracting,

Atrium relaxing then

Atrium tense and full,

Atrium emptying,

tricuspid valve open

filling, tricuspid closed

tricuspid closed

tricuspid open

wave

Figure 5-1: Jugular Venous Pulse

5-9

5-10

HYPERTENSION

Table 5-4: Venous Waveforms in a Cltnlcal Setting Neck Vein Appearance

Condition Pulmonary HTN

Elevated

Tricuspid regurgitation

Large

Constrictive pericarditis

Rapid x andy descents

Kussmaul sign, pericardia! knock

Tamponade

Rapid x descent

Pulsus paradoxus, hypotension

Tricuspid stenosis

Slow y descent

T S murrnur

Restrictive cardiomyopathy

Rapid x andy descents

Low-voltage ECG, echo, myocardial biopsy

Tension pneumothorax

Distended neck veins

and

waves

Other Diagnostic Features Other physical exam findings of pulmonary HTN

waves

TR murmur, pulsatile liver

Dyspnea, unilateral absent breath sounds, deviated trachea, chest x-ray

Unilateral distended neck veins

Facial edema and cyanosis, diagnosis of cancer

AV dissociation

Irregular canrion

ECG

RV infarction

Elevated

wave

Superior vena cava syndrome

ASD

Large

and

waves

Acute inferior Ml, Kussmaul sign

waves and rapid

Fixed split S2, echo

y descent

HYPERTENSION Suspect

secondary causes

CARDIAC ISCHEMIA

hypertension

(HTN)

in patients who develop HTN before age 30 years, who have drug-resistant HTN, or who develop uncontrolled HTN that was previously well controlled. Systolic abdominal bruits (without a diastolic bruit) suggest renal vascular hypertension. Bilateral renal artery stenosis (RAS) can lead to severe exacerbation of hypertension and decline in renal function with initiation of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). Noninvasive tests to diagnose RAS include duplex ultrasonography,

OVERVIEW Angina is chest pain caused by a "supply-demand" mismatch between coronary perfusion and cardiac workload. It is typically classified as either stable or unstable (pain at rest, new onset or increased frequency). Obstructive

atherosclerotic

coronary

artery

lesions

(supply problem) are the most common cause of stable angina (Image

5-5). Plaque rupture or erosion with

superimposed thrombus is the most common underlying process triggering acute coronary syndrome (ACS).

CTA (in individuals with normal renal function), and

There are many causes of increased demand (e.g.,

magnetic resonance angiography (MRA). When clinical

tachycardia,

suspicion is high and results of noninvasive tests are

other causes of a decreased supply (e.g., hypotension,

inconclusive, catheter angiography is recommended

coronary vasospasm, anemia, and hypoxia). Coronary

to diagnose RAS. patient with hypokalemia and low renin. of

pheochromocytoma

and

thyrotoxicosis)

and

many

blood flow can be impaired in conditions such as severe

Think of primary hyperaldosteronism in a hypertensive Think

fever,

hypertensive

with recurrent and intermittent episodes of severe hypertension, frequently accompanied by palpitations and severe apprehension. Much more on hypertension in Nephrology, Book 2.

aortic valve disease with left ventricular hypertrophy

(LVH), hypertension, idiopathic dilated cardiomyopathy, and hypertrophic cardiomyopathy, even in the absence of epicardial CAD. Note: Only

20% of patients actually have classic

angina at the moment of ischemic ST changes. Silent myocardial ischemia is painless but just as harmful as angina-associated ischemia. Silent ischemia is seen frequently in diabetic patients as well as those with prior ischemic events.

CARDIAC MEDICATIONS

Silent ischemia, myocardial

infarctions, and thrombotic strokes tend to occur in a circadian pattern, with the highest incidence in the early

Refer to Table

5-5 for an overview and comparison of

commonly used cardiac medications. Pay attention to those that prolong survival!

morning hours. The distinction between stable and unstable angina is a key factor in determining management/diagnostic strategies. Short- and long-term risk (death and MI) in patients with acute coronary syndrome is much higher

ÂŠ 2014

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CARDIAC ISCHEMIA

•

True or false? A systolic abdominal bruit without a diastolic bruit suggests renal vascular hypertension.

•

What time of day does the highest incidence of spontaneous ischemic cardiac events occur?

than in patients with stable angina, and therefore patients with ACS warrant emergent medical attention, inpatient management, and, much more commonly, revascular ization. (See Acute Coronary Syndrome on page

5-14.)

Stable angina, on the other hand, is generally evaluated in the outpatient

setting

and

symptoms

are often

managed medically. The most important, easily determinable prognostic

Image 5-5: Angiogram showing narrowing in coronmy artery.

factor in patients with coronary artery disease is the degree of LV dysfunction. (If severe, it can be a reflection of multi-vessel or left main/left main-equivalent disease.)

Table 5-5: Common Card1ac Medications Negative

Negative

Vaso-

Anti-

Prolong

lnotrope

Chrono-

Dromo-

dilator

anginal

Survival

Survival in

trope

Post-MI

Systolic HF, arrhythmias

+++

HTN, angina, HF, arrhythmias

C arvedi\ol

+++

HTN,�gina, HF, arrhythmias

Nifedipine

HTN, angina

Y(in DCM)

HTN, angina, DCM

Diltiazem

HTN, angina, arrhythmias

Verapamil

+++

Nitrates

Y(with hydralazine)

Angina, HF

ACEis

HTN,HF

ARBs

HTN,HF

Y(with nitrates)

HTN,HF

Medication

Digoxin Beta-blockers

Amlodipine

,�

Indications

Hydralazine

Spironolactone

HTN,HF

Eplerenone

Y(w/HF)

Y(pMI}

HF postMI

N ,...,

5-11

5-12

CARDIAC ISCHEMIA

to work by inhibiting the late sodium current in cardiac

Table 5-6: Bruce Protocol Stage

Min

%Grade

MPH

METs

1.7

4.7

2.5

7.0

3 .4

10.1

I 2

myocytes, thereby reducing sodium and calcium over

3 4

4.2

12.9

5.0

15.0

load that follows ischemia. This improves myocardial relaxation and reduces left ventricular diastolic stiffness, which in turn enhances myocardial contractility and perfusion. More on anti-anginal drugs: •

all decrease myocardial 02 demand, and all decrease afterload.

The exercise tolerance test is an excellent, objective way

•

Nitrates decrease preload more than afterload and also dilate coronary vessels. Acute preload reduction

to determine the severity of angina and to determine

is why nitrates can cause severe decompensation

prognosis. Patients who are able to go to stage 4 of

in patients with an acute right ventricular MI.

Bruce protocol (Table 5-6) have a nearly 100% 5-year

(Remember, do not give nitrates during acute RV

survival, while those who cannot get past stage I

infarct.) Patients on nitrates get a sympathetic reflex

have only a 50% 5-year survival! Note that coronary

increase in heart rate (HR). Nitrates are degraded in

angiography is not required for the determination of

the liver. Tolerance develops rapidly with nitrates

either of these prognostic factors!

(tachyphylaxis), but you can avoid tolerance by

Spasms of the coronary arteries usually show up as

having a 6-hour "nitrate-free window" once a day;

transient ST-segment elevation if they occur during

i.e., between midnight and 6 a.m. Development of

stress testing.

tolerance is less likely with mononitrates than with dinitrates.

What causes resting ST-segment elevation? Acute Ml, pericarditis, LV aneurysm, LBBB, ventricular pacing,

•

LVH, and benign early repolarization.

Beta-blockers complement nitrates well because they decrease the reflex tachycardia.

myocardium. There is no irreversible myocyte injury. When perfusion is restored to normal, contractility

•

with angina/ischemia and hypertension. See

Reperfusion injury occurs when a severely ischemic �

Table 5-5. Verapamil and diltiazem should be

I hour, causing

used cautiously, if at all, in patients with systolic

further irreversible microvascular damage and damage

heart failure due to the negative inotropic effects.

to the myocardial cells.

Short-acting nifedipine is contraindicated due to steep drops in BP and reflex tachycardia.

Stunned myocardium is also the result of acute ischemia.

From the time perfusion is restored, it can take 7-10 days

•

for the ventricular function to return to normal. such

anemia,

There is a high probability of coronary thrombus formation with unstable angina, so always use either IV heparin or subcutaneous low-molecular-weight

Treatment of all angina: ModifY risk factors and correct factors

Calcium antagonists: The combined vasodilatory and antihypertensive effects make them ideal for patients

should return to normal. myocardium is reperfused after

Beta-blockers decrease myocardial 02 demand by decreasing HR, blood pressure (BP), and contractility.

Hibernating myocardium is chronically underperfused

aggravating

Nitrates, beta-blockers, and calcium channel blockers

heparin (LMWH) if there are no contraindications.

hypertension,

smoking, drug abuse, and noncompliance. (Good luck!)

The following are now recommended concomitantly with heparin and for follow-up medical therapy for unstable angina:

ANTI-ANGINAL DRUGS Beta-blockers and nitrates are the staples of medical

treatment, but calcium channel blockers can also help. Nifedipine and amlodipine decrease angina by

•

Aspirin daily for life

•

Clopidogrel x I month and ideally up to a year (particularly if a stent is placed)

both coronary artery vasodilation and peripheral vaso dilation (decreases workload). The main anti-anginal

EVALUATION OF

effect of diltiazem and verapamil is due to their negative

CHRONIC STABLE ANGINA

chronotropic effect. ASA decreases mortality and MI occurrence in unstable (and probably stable) angina. Use clopidogrel (Plavix®) in patients who cannot tolerate or are allergic to ASA or who have an indication to take this in addition to ASA. Ranolazine (Ranexa®) may also have a role in some

patients with persistent angina on maximal standard therapy, or as a substitute for beta-blockers. It is thought

Note The following is drawn from the 2012 ACC/AHA guidelines. First and foremost is the involvement by an informed patient: Choices about diagnostic and thera peutic options should be made through a process of shared decision making involving the patient and phy sician, with the physician explaining information about risks, benefits, and costs to the patient.

CARDIAC ISCHEMIA

can accelerate atherosclerosis, enhance platelet aggregation, cause vasospasm, and increase myocardial oxygen demand. • •

•

What does ST-segment elevation suggest on an

symptoms in the presence of coronary obstruction or,

exercise ECG stress test?

when severe, cause angina in the absence of coronary

What are causes of resting ST-segment

obstruction by:

elevation? •

The following comorbid conditions can precipitate

Explain the similarities and differences between

valvular disorder, aortic stenosis, or HCM

hibernating myocardium, reperfusion injury, and stunned myocardium. •

What are the main drugs used to treat angina?

•

Which patient might ranolazine (Ranexa®) benefit?

•

hypoxemia, and increased blood viscosity From the above, determine if the patient has high, intermediate, probability

or needs

low no

probability further

CAD.

Low

testing.

Those

with

oxygen demand?

"risk stratification" with further testing (discussed next).

•

Which anti-anginal drugs decrease preload?

•

What anti-anginal drug do you not give to a patient with RV infarct? Why? Why should you determine the probability of CAD in a person with intermittent chest pain? For which patient with chronic stable angina do you do an echocardiogram? Why?

•

Decreasing myocardial oxygen supply: anemia,

intermediate or high probability of CAD should undergo

Which anti-anginal drugs decrease afterload?

•

Which anti-anginal drugs decrease myocardial

•

Increasing cardiac demand: hyperthyroidism, cocaine use, severe uncontrolled HTN, significant

A patient undergoing a workup for chronic stable angina is determined to be at high risk for death. What is the next step?

Evaluation of a patient with chest pain is a 3-step process: I ) Determine the probability of CAD.

2) Noninvasive testing for diagnosis and risk stratification. 3) Additional workup based on estimated risk.

2. Noninvasive Tests for Chronic Stable Angina: Diagnosis and Risk Stratification

ECG: especially for checking ST-T wave changes that suggest ischemia, Q waves, and LVH. Other findings (e.g.,

RBBB,

LBBB,

atrial fibrillation, bifascicular

block) are not specific indicators of CAD.

Chest x-ray is done only if there are signs of heart failure (HF), valvular disorders, or pericardia! disease.

Exercise testing is the most important test in risk stratification. See Tab l e 5-1 on page 5-5 to review how to pick the best stress test for your patient. And remem ber, for those who can exercise, do exercise testing for all with stable angina. Exercise capacity is one of the stronger indicators of long-term risk. For this reason, it is preferable to perform exercise stress if the patient is able to achieve maximal workload. In addition, exercise can provide a

1. History and Physical Exam:

higher physiological stress than would be achieved by

Determine Probability of CAD

pharmacological testing.

First assess the probability of coronary artery disease

Assess LV systolic function (generally with echo)

(CAD). Factors used in the assessment include type of chest pain (typical, atypical, nonanginal), age, gender, risk factors (particularly diabetes mellitus, smoking, and hypertension), and ECG abnormalities (Q waves and ST abnormalities). This step is very important because it determines pretest probability for the rest of the tests, which improves the positive and negative predictive values of these tests. After other causes of chest pain are ruled out, determine the following: •

Typical vs. atypical chest pain is determined by assessing quality, location, and duration of the chest pain. Also, what precipitates or relieves the pain?

•

Cardiovascular risk factors: especially DM, HTN, smoking, hyperlipidemia, family history of CAD, and postmenopausal status in women. History of substance abuse must be obtained. Cocaine

2014 MedStudy

only in patients with prior MI, pathological Q waves, symptoms or signs suggestive of heart failure, arrhyth mias, or heart murmur. If the test results won't change management (severe comorbid conditions that preclude possibility of revas cularization or patient does not want revascularization), do not order.

3. Determination of Further Workup in Chronic Stable Angina Based on stress test results, determine the probability of death or Ml and stratify patient into a high-risk

(> 3%/year), intermediate-risk (1-3%/year), or low (< I %/year). Patients with high risk should

risk group

be referred for coronary angiogram. Patients with low or intermediate risk should be treated with medical

5-13

5-14

ACUTE CORONARY SYNDROME

therapy to improve symptoms and function, and further

•

workup can be deferred if symptoms can be controlled

Stepwise strategy smoking cessation (ask, advise, assess, assist, arrange, avoid), avoidance of exposure

with medical therapy.

to environmental tobacco smoke.

Low-risk patient: low-risk Duke treadmill score (2 5)

•

Weight loss.

indicating good exercise capacity with no signs of

•

Blood pressure management (goal< 140/90):

significant ischemia, normal stress echo, or normal or

ACEI/ ARB and/or add thiazide diuretics or calcium

small myocardial perfusion defect.

channel blockers if needed to obtain goal BP.

High-risk patient: high-risk Duke treadmill score (:S -I 0), inducible wall motion abnormalities stress echo, stress induced

2 segments on

•

Influenza vaccine annually.

•

Statin in all patients (if no contraindications/

•

Antiplatelet therapy: aspirin 75-162 mg/d indefinitely;

adverse effects).

perfusion abnormalities

2 10% of myocardium on MPI, or severely reduced left

clopidogrel when aspirin is contraindicated.

ventricle (LV) systolic function. If a patient has an intermediate-risk treadmill score

•

Beta-blockers: started and continued for 3 years in all patients with normal LV function. Continue

(score between -I 0 and +5), stress imaging should be

indefinitely ifLVEF < 40%. Use carvedilol,

considered to further assess risk. Again, stress testing is

metoprolol succinate, or bisoprolol in all patients

not as useful for low-risk (false positives) and high-risk

withLVEF< 40%, unless contraindicated.

patients (false negatives). •

ACEis in all patients who also have hypertension, diabetes mellitus, LVEF < 40%, or chronic kidney

TREATMENT OF CHRONIC

disease, unless contraindicated (ARB if ACE!

STABLE ANGINA

intolerant).

Objectives of treatment of chronic stable angina include reduction of premature cardiovascular death, prevention

CARDIOVASCULAR DISEASE (CVD}

PREVENTION IN WOMEN

complications

including

and

heart

failure,

complete or near complete elimination of symptoms, and improvement of functional capacity and quality of life. Medical therapy to prevent Ml and death:

A 2011 update of the AHA Guidelines for CVD Prevention in Women warns that: •

Hormone therapy should not be used as primary or

•

Antioxidants (i.e., vitamin C, E, beta-carotene) should

secondary prevention.

•

Antiplatelet therapy: aspirin (clopidogrel if aspirin is

•

High-dose statin

•

Folic acid or vitamin B6 should not be used.

•

Beta-blockers (if left ventricular ejection fraction

•

Garlic, coenzyme Q10, selenium, or chromium

•

Do not use aspirin in healthy women< 65 years of

contraindicated)

not be used as primary or secondary prevention.

[LVEF] < 40% or prior MI) •

should not be used.

ACE inhibitors (ifLVEF< 40%, DM, HTN, or CKD)

age for primary prevention of MI. (Aspirin is okay for those 2 65.)

Medical therapy for relief of symptoms: •

Beta-blockers as initial therapy.

•

Prescribe calcium channel blockers or long-acting nitrates when beta-blockers cannot be used, or in combination with beta-blockers when beta-blockers are not sufficient.

•

are drawn. [Know this well!]

risk who remain significantly symptomatic should be referred for coronary angiogram to define coronary anatomy.

Acute coronary syndrome (ACS) is generally caused by atherosclerotic plaque rupture, fissuring, erosion, or a combination with superimposed intracoronary thrombosis; results in acute ischemia; and is associated with an increased risk of cardiac death and myocardial

Compilation of all recommendations: Diet: Limit saturated fats (to< 7% of total calories), eliminate trans fats, and limit cholesterol intake

•

CLASSIFICATION OF ACS This is another area from which many exam questions

Ranolazine in combination with beta-blockers.

High-risk patients and patients with low or intermediate

•

ACUTE CORONARY SYNDROME

infarction. Acute coronary syndrome is composed of 2 types:

(to< 200 mg/d).

1) Unstable angina (UA) or non-ST elevation

Physical activity: 30-60 minld of moderate-intensity

2) ST elevation

aerobic activity for 5-7 d/wk.

UA/non-ST elevation ACS includes unstable angina (UA) or non-ST elevation Mis (NSTEMis). You will see these terms combined as UA/NSTEMI.

ACUTE CORONARY SYNDROME

Inferior vs. anterior MI: Inferior Mis are associated with more stable arrhythmias, such as junctional escape and

... uiz •

Mobitz I, instead of the poorer prognosis with Mobitz

2 and bundle-branch blocks (BBBs), which are more often seen in anterior Mls. Even when Mobitz 2 or com

Would you recommend aspirin in a healthy woman

plete heart block is seen in an inferior MI, it is usually

65 years old for primary prevention

temporary. Also, the amount of infarcted myocardium is

ofMI?

typically larger with anterior Mls. Unfortunately, septal

•

What are the 2 major categories of ACS?

•

Name 1 group of patients that is more likely to

rupture can occur in either type. (See Complications of Myocardial Infarction on page 5-22.)

present with Ml without chest pain. •

How are troponin I and T used? How long do

MARKERS FOR AMI

they stay elevated after an Ml?

Serum

markers

that

increase in

response

to acute

myocardial necrosis include troponins, creatine kinase

ST elevation ACS is ST elevation Mls (STEMis).

myocardial bands (CKMBs), and myoglobin (Table

R arely, ACS can be due to occlusion by coronary emboli, congenital abnormalities, coronary spasm, and

[Know all of the following!] Assays

a wide variety of systemic inflammatory diseases. Terms "Q wave" and "non-Q wave MI" are no longer used.

5-7).

detect

components

cardiac

muscle,

troponin I and troponin T (cTni and cTnT), are now the gold standard for the detection of myocardial necro sis. The level of either of these also has been shown to

Patients with NSTEMis have a smaller size of infarcted

have prognostic implications in the setting of an acute

area and decreased early mortality compared to those

MI. The 2 troponin assays are equally useful, and local

with STEMis, but a higher risk for persistent angina,

preferences dictate which one is used.

reinfarction, and death within several months! This is due to the diffuse coronary disease more commonly seen in NSTEMI patients.

Troponins first become elevated at 4 hours following an MI and peak at about 44 hours after the event. They can remain elevated for 10-14 days after an MI, which

So, although NSTEMis have a lower early mortality,

can muddy the picture in those suspected of having a

they have a higher 6-month mortality compared to

recurrent MI-use myoglobin and/or CKMB instead

STEMis. Also, know that patients with NSTEMis are more likely than those with STEMis to have had a prior Ml or angina! Differential includes: carditis,

of those who present more than 24-48 hours after onset

diagnosis ACS

(see below). On the other hand, because they do stay elevated so long, troponins are beneficial in the workup

(MI),

esophageal

prolonged

aortic biliary

pain

of symptoms.

peri

Be aware that troponins can also be elevated in chronic

problems,

renal failure, myopericarditis, HF, sepsis, pulmonary

chest

dissection, tract

pneumothorax, pulmonary embolism, pleuritic pain related to pneumonia, musculoskeletal inflammation,

embolism, and cardiac trauma. In addition, troponins can be elevated with RV strain causing microvascular dys

and psychogenic causes.

function. Although troponins are sensitive markers for

NOTES

specific; therefore, they are good for excluding AMI but

acute myocardial infarctions (AMI), they are not highly

15% of acute myocardial infarctions (AMls) are asymptomatic. MI without chest pain or with atypical chest pain is more common in the following: •

Elderly (about 2/3 of these patients> 75 years of age)

•

Diabetics

•

Women

•

Those with prior CAD

Mitral regurgitation due to papillary muscle dysfunction is seen more commonly with inferior Mls. Ventricular septal defect (VSD) from septal rupture is seen more commonly with anterior and inferior Mls. Arrhythmias in the first 48 hours after Mls are due to acute ischemia (or are reperfusion-related) and do not imply a need for long-term antiarrhythmic therapy.

2014 MedStudy

not as good for confirming one. Sensitive but not specific. CK and its isozyme CKMB have been the traditional

markers of choice for myocardial necrosis. CK is a nonspecific marker of muscle injury (both skeletal and Table 5-7: Acute Myocardial lnfarct1on Markers Marker

Initial

Peak

Return to

Elevation

Normal

Myoglobin

1-4hr

6-7hr

24 hr

Troponin I

4hr

44hr

10-14d

CKMB

3-12 hr

24 hr

2-3 d

CKMB

2-6 hr

18 hr

(rule of 4s!)

isoform

5-15

5-16

ACUTE CORONARY SYNDROME

myocardial), while CKMB is specific to myocardium. These become detectable at 3-12 hours following an Ml event and peak at 24 hours. CKMB typically returns to normal range after 48-72 hours, earlier than the troponins. Both CK and CKMB can be elevated due to non-MI causes, such as in rhabdomyolysis. The CKMB:total CK ratio can be useful to distinguish between cardiac and noncardiac sources of CK elevation-although this is not fully reliable in very severe cases of muscle injury. Myoglobin is a very sensitive, but nonspecific, test for

acute myocardial necrosis. It rises very rapidly, so a

TREATMENT OF ACS Overview In general, the sequence to addressing acute coronary syndrome is to first take proper care of the patient prior to arrival in the emergency department. Once the patient arrives, do an assessment, do an ECG, and draw labs. Based on these results, determine if the patient with sug gestive symptoms is actually having an ACS. Figure 5-2 diagrams this process of determining if the patient has ACS.

negative myoglobin in the first few hours is useful in

Figure 5-3 diagrams the process of managing UA/

ruling out an infarction (high negative predictive value).

NSTEMI ACS vs. ST-elevated ACS.

Because it is excreted quickly in the urine, myoglobin is also the quickest to return to normal-within 24 hours so it can be potentially useful to help evaluate recurrent chest pain soon after an Ml, when troponins and CKMB

lf the patient has definite ACS, pursue I of the following protocols: •

frequently used in clinical practice.

•

Acute MI Treatment Pathway with STEMI or New LBBB (Figure 5-5 on page 5-21)

The most sensitive and specific markers now used are a combination of troponin I or T and CKMB.

Acute Ischemia Treatment Pathway-UA/NSTEMI (Figure 5-4)

are still elevated. Because of its low specificity, it is not

Now, let's go through these steps in more depth.

With both the troponins and CKs, the overall trend is important and gives added information beyond a single elevated value ("trending enzymes"). An individual whose enzymes continue to rise is a very different patient from someone whose enzymes peaked earlier in

Prehospital Management 2013 ACC/AHA guidelines for chest pain: •

the day, even in the absence of symptoms!

Call 911 and transport to hospital by ambulance (rather than friends/relatives): EMS can diagnose STEMI earlier with prehospital ECG and prefer entially transport to PCI -capable hospital (shorter reperfusion times and lower mortality), and can treat cardiac arrest en route.

•

Possible ACS with

Give nonenteric coated ASA ( 162-325 mg) as bite and chew xI.

nondiagnostic ECG and normal initial serum markers

•

Nitroglycerin (tablets or spray): If the drug is avail able, give only 1 dose, then:

Observe; follow up at 4-8 hrs; recheck ECG

Unimproved or worsening-give no more; call 911.

Improved--can repeat to max of 3 doses (at 3-5-minute intervals).

cardiac markers

...

No recurrent pain

Recurrent pain;

and negative f/u studies x

+flu studies

12 hours

Definite ACS

No ST elevation but

Stress study to provoke ischemia; consider evaluation of

+ ST and/or T wave changes,

LV function

if ischemia is present

--,

Positive

(these tests done before

Negative

Probable diagnosis is nonischemic discomfort; pt at low risk for ACS

outpatient follow-up

or new

LBBB

+ cardiac markers, or + hemodynamic abnormalities Diagnosis of

I .

UA/NSTEMI ACS

D1agnos1s of

Evaluate for

confirmed

UA/NSTEMI ACS

reperfusion

con

Admit to hospital and

Arrange for

ST elevation

+ ongoing pain, or

discharge or as outpatient)

�

therapy

+ Follow guidelines

manage with the

manage using the

for STEMI or

Acute Ischemia Pathway

new

(see Figure 5-5)

(see Figure 5-6)

Figure 5-2: Diagnostic Pathway for Possible ACS

LBBB

Figure 5-3: lnittal Tx Pathway for Definite ACS

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ACUTE CORONARY SYNDROME

High-risk features include all of the following:

Q�uiz •

What are the prehospital guidelines for chest pain?

•

Ongoing chest pain for longer than 20 minutes

•

Reversible ST-segment changes of at least 0.5 mm

•

Elevated cardiac enzymes

•

Signs of LV dysfunction

What happens next depends on the ECG:

What are the major things you should do in early risk stratification of a patient who presents with ACS in the emergency department?

•

If the ECG is abnormal: Follow guidelines

•

If the ECG is nondiagnostic: Repeat the ECG q

(see below).

Based on early risk stratification of ACS, to what

3 groups can a patient be assigned?

15-30 minutes or do continuous monitoring. Note: An acute MI involving the left circumflex can still

Note: If the patient has taken a phosphodiesterase-S

present as a nondiagnostic (or normal) 12-lead ECG;

inhibitor (e.g., sildenafil or vardenafil) within

consider obtaining V7-V91eads.

24 hours (48 hours for tadalafil), do not give

Based on this early assessment, assign patients to 1 of

nitroglycerin due to the risk of severe hypotension! •

ECG in the field by EMS.

•

Be prepared to recognize and manage ventricular

the following 3 groups in the ACC/ AHA protocol: 1) Noncardiac chest pain or chronic stable angina: Treat

arrhythmias.

accordingly.

Evaluation of Patients with

Possible ACS with nondiagnostic ECG and normal initial serum markers (Figure 5-2): Observe at least

Symptoms Suggestive of ACS Early evaluation:

12 hours following symptom onset. If there is no

For patients who

recurrence of symptoms, a 2nd set of markers is nega

present to the

tive, and an ECG is unchanged, perform further risk

emergency department with symptoms suggestive of

stratification with an appropriate stress test. Patients

ACS, immediately (within 10 minutes) get an ECG,

who have a negative or low-risk stress test can be

draw blood for cardiac markers, give aspirin if not con

discharged to home and followed as outpatients

traindicated, and conduct a directed history and physical

(green box in Figure 5-2). If the observed patients

examination.

have recurrent symptoms, subsequent positive cardiac

Acute ischemia pathway (UA or NSTEMI):

Early invasive

Give aspirin,

•

Give UFH, enoxaparin, or bivalirudin. Fondaparinux okay if no invasive tx.

•

Give clopidogrel or prasugrel if ASA-intolerant. Prasugrel not for conservative tx.

•

Abciximab (GP lib/lila) only if immediate PCI.

•

NO FIBRINOLYTICS!

•

Monitor for rhythm and ischemia.

1 therapy

02 prn, beta-blocker, nitrate prn.

•

• Early conservative therapy

Recurrent symptoms , ischemia , heart failure , serious arrhythmia

12-24 hour

Patient stabilizes; do stress test or evaluate

EF <

40%

angiography

Immediate

LV fn

I 1

Evaluate function

I I

EF �

40%

angiography

Not low risk

I I

Stress test

Low Risk

I Figure 5-4: Acute Ischemia Treatment Pathway-

UAor NSTEMI

Follow on medical Tx

5-17

5-18

ACUTE CORONARY SYNDROME

markers, ECG changes, or a positive stress study, admit and manage according to the acute ischemia pathway (Figure 5-4).

Defmitive ACS: immediately determine whether there is ST-segment elevation or new LBBB (Figure 5-3): •

Patients without ST-segment elevation or new LBBB should be admitted and treated according to the acute ischemia protocol.

•

Patients with ST-segment elevation or new LBBB should be considered for emergent reperfusion

Anticoagulant I Antiplatelet Therapy in ACS Overview Intense

and

parenteral

anticoagulant

recommendation for ACS.

Parenteral Anticoagulants The parenteral anticoagulants are unfractionated heparin (UFH),

therapy.

antiplatelet

therapy with multiple agents is a major treatment

enoxaparin,

fondaparinux,

and

bivalirudin.

One of these agents is recommended for most patients

We will discuss each of these scenarios shortly, but first let's talk about general measures considered for all

with ACS: •

UFH is preferred if coronary artery bypass graft (CABG) is anticipated within 24 hours (or coronary

patients with ACS.

angiography, although this is not as absolute).

ACS: GENERAL MEASURES

•

mind that the dose should be adjusted in the patient

ECG, NTG, Morphine, Beta-Blockers, ACEis, Atropine General anti-ischemic measures for all patients with ACS include: •

•

with renal impairment. •

Fondaparinux can be considered if the patient has increased risk of bleeding, especially if a conservative (noninvasive) strategy is chosen for the patient. It is not used if percutaneous coronary intervention (PCI)

Continuous ECG monitoring

is expected (due to increased risk of catheter throm

Aspirin

bosis and increased coronary complications). If it

Sublingual nitroglycerin (NTG) spray x

3 pm for pain

and I V NTG for continued ischemia or hypertension •

Enoxaparin is commonly used; however, keep in

Morphine if pain is not relieved by NTG

is in use, and invasive angiography/PCI is planned, switch to another agent, such as UFH or bivalirudin.

Oral beta-blocker and an ACEI if the patient is still

Antiplatelet Therapy

hypertensive or has evidence of LV dysfunction (EF

Aspirin

<40%) Supplemental oxygen should be administered to patients with UA/NSTEMI with an arterial saturation < 90%, respiratory distress, or other high-risk features for

Administer aspmn at a dose of 162

measurement of s.02.) It is reasonable to consider sup

Thienopyridines- Platelet

plemental oxygen during the first 6 hours of any ACS;

Blockade

vascular resistance! by blocking

Thienopyridines

include

P2Y12 Receptor

clopidogrel

(Plavix®),

and

prasugrel (Effient®). Their effect is additive to aspirin.

Note: Beta-blockers reduce myocardial 02 consumption. Also,

indefinitely unless there are contraindications.

hypoxemia. (Pulse oximetry is useful for continuous

however, supplemental oxygen can increase coronary

or 325

immediately to all patients with ACS, and continue

the

often-excessive sympathetic

activity, they reduce the load on the heart and decrease the likelihood of arrhythmias. Oral use is preferred.

These drugs block the ADP receptor P2Y12 on platelets. Ticlopidine is no longer routinely used due to its side effect profile. Interaction between proton pump inhibitors (PPis) and

Contraindications to beta-blockers include bradycar

thienopyridines was thought to be a problem, but latest

dia, hypotension, 2"d or 3rct degree AV block, pulmonary

studies do not prove a cause and effect relationship.

edema, and asthma. Caution should be used in giving

PPis are not contraindicated with thienopyridines, but

beta-blockers to patients with signs of acute heart fail

consider the risks/benefits if using concomitantly.

ure. (See Beta-Blockers on page 5-52). Non-dihydropyridine

calcium

channel

Clopidogrel requires a liver enzyme (CYP2C19) to blockers

become active. Overall, 2-14% are poor metabolizers:

( verapamil or diltiazem) can be given if beta-blockers

2-5% of African-Americans and Caucasians and up to

are contraindicated and the patient continues to have

20% of Asians. There are genetic tests that can check

ischemia and hypertension but no LV dysfunction.

for this issue. In 20 l 0, clopidogrel (Piavix®) received

Atropine is indicated for the temporary management of acute sinus bradycardia with signs of low cardiac output while preparing for temporary pacing. Bradycardia

an FDA boxed warning about poor metabolizers and the tests available, but genetic testing is not recommended in any current guideline.

associated with MI (usually inferior Ml) may be

Prasugrel is a thienopyridine that has a faster onset of

temporary, and atropine alone may be sufficient.

action and is effective in clopidogrel-resistant patients. It has significantly more antiplatelet activity and therefore

ACUTE CORONARY SYNDROME

ACS: MANAGEMENT OF UA I NSTEMI -THE ACUTE ISCHEMIA PATHWAY Early Invasive vs. Conservative Therapy •

•

What anti-ischemic measures are done initially

Note: The 2012 update of the ACC/AHA UA/NSTEMI

for all patients with ACS?

treatment guidelines have 2 areas of focus (Figure

Which patients should receive a platelet GP lib/

on page

lila inhibitor? •

Of those with ACS, what group gets considered

Antithrombotic therapy with multiple agents

2) Aggressive use of early cardiac catheterization in those

for fibrinolytic therapy and what group definitely

with moderate-to-high risk

does not? •

Regarding UA/NSTEMI treatment:

Under what conditions is angiography/PCI considered for those with UA!NSTEMI?

•

Use antiplatelet therapy, such as clopidogrel, prasugrel, or ticagrelor for at least

lower cardiovascular events-but also higher rates of Clopidogrel and prasugrel can be used interchangeably for all proven ACS scenarios except if CABG

year after receiv

ing a drug-eluting (DES) or bare-metal stent (BMS)

significant bleeding and is contraindicated in the elderly.

and at least I month without a stent (for up to a year). •

Note: If a patient needs surgery, do not stop clopidogrel, prasugrel, or ticagrelor until at least

6 months and preferably 1 year after DES placement.

imminent (operative bleeding complications).

Similarly, do not stop these agents until at least 30 days after BMS placement. Withholding

Nonthienopyridines- Platelet P2Y12 Receptor

clopidogrel, prasugrel, or ticagrelor and performing

Blockade

surgery prior to these time frames has an increased risk of death and in-stent thrombosis.

Ticagrelor (Brilinta®), a nonthienopyridine, is a recently

approved reversible oral antagonist

5-4

5-17):

the

platelet

P2Y12 receptor with a rapid onset of action. Similarly

•

Intense lipid and BP control is recommended.

•

Stop all nonsteroidal antiinflammatory drugs

to prasugrel, it is more effective than clopidogrel with no difference in overall bleeding. It can be used as an alternative to clopidogrel/prasugrel. Glycoprotein lib/lila Inhibitors

(NSAIDs)-except ASA-during hospitalization. Okay, you have determined the patient is having ACS and have initiated treatment according to the general measures on the prvious page. You've drawn labs and done the ECG, which reveals no acute ST changes.

Glycoprotein (GP) Ilblllla inhibitors act on the final

The labs come back, and you determine that the patient

common pathway of platelet aggregation-where fibrin

has

binds platelets together by connecting to the GP lib/Ilia

(markers normal).

receptor. The most studied drug is abciximab. Others

You have 2 options:

are eptifibatide, tirofiban, and lamifiban. Only the IV

NSTEMI

(cardiac

markers

abnormal)

forms are effective. GP lib/lila inhibitors are considered

I) Early invasive therapy (angiography)

for high-risk ACS patients (elevated troponin, hemo

2) Early conservative therapy

dynamic instability, dynamic ECG changes); however, since introduction of dual oral antiplatelet therapy they are used less commonly.

Fibrinolytic Therapy in ACS Do not give fibrinolytic therapy to patients with UN NSTEMI because it increases mortality. Do give fibrino

Early Invasive Therapy in UA I NSTEMI Urgent invasive therapy for UA/NSTEMI indications: •

HF or hemodynamic instability

•

Recurrent or refractory angina

•

Life-threatening arrhythmias

lytic therapy to those ACS patients with STEMI or new

Invasive therapy for UA/NSTEMI within 24-48 hours

LBBB if immediate PCI is not available and if there are

indications:

no contraindications (discussed later). •

Antiarrhythmic Drugs in ACS Give lidocaine only if the patient has ventricular fibril lation/tachycardia. Prophylactic lidocaine is harmful. Lidocaine has an increased half-life in patients with heart failure (HF) and those on propranolol. Amiodarone is the current drug of choice for ventricular tachycardia and ventricular fibrillation.

Elevated cTnl or cTnT

•

Dynamic ST changes

•

Diabetes

•

GFR

•

40%

•

Early post-MI angina

•

PCI within the previous 6 months

•

Prior Ml

60 mL!min

5-19

5-20

ACUTE CORONARY SYNDROME

•

Prior CABG

•

Intermediate/high-risk patients (either by clinical

Bare-metal stent (BMS):

judgment or using a scoring system such as the TIMI risk score)

•

ASA 162�325 mg/d x 1 month, then 75�162 mg/d

•

Clopidogrel, prasugrel, or ticagrelor x 1 month to

for life 1 year

All UA/NSTEMI patients selected for early mvas1ve therapy get the following medical therapy: •

Drug-eluting stent (DES):

Parenteral anticoagulant: o

UFH, enoxaparin, or bivalirudin. Do not give

ASA 162�325 mg/d for 3-6 months, then

•

Clopidogrel, prasugrel, or ticagrelor for at least

75�162 mg/d for life.

fondaparinux due to increased rate of catheter thrombus formation. •

•

1 year. Consider continuing for longer than a year.

Antiplatelet therapy: o

ASA plus either clopidogrel, prasugrel, or ticagrelor (dual therapy). Note: Do not use prasugrel for patients with prior history of stroke/transient isch

Cocaine and Methamphetamine Users with ST Elevation

emic attack ([TIA]; use clopidogrel in these cases).

Give

GP lib/lila inhibitor can be given if the patient is

benzodiazepines (not beta-blockers):

high risk. Remember:

•

UA/NSTEMI

patients

not

nitroglycerin, calcium

channel

blockers, and

If ST-segments are elevated and there is no immediate improvement with treatment, proceed with coronary

receive

angiogram or fibrinolytics if cath lab is not available.

fb i rinolytic therapy. •

If chest pain resolves with treatment, troponin is not elevated, and there are no ST-T abnormalities, patient

Early Conservative Therapy in UA I NSTEMI

does not need stress test.

Patients with UA/NSTEMI who respond to intense

•

Avoid beta-blockers.

medical therapy, have none of the high-risk features listed under invasive therapy above, and do well on post

ACS: MANAGEMENT WITH STEMI OR

ACS stress testing are at low risk for immediate and

NEW LEFT BUNDLE-BRANCH BLOCK

1-year mortality-and can be followed without invasive

Note

evaluation.

The management of acute coronary syndrome (ACS)

Conservative therapy for UA/NSTEMI patients: •

for those with ST elevation MI (STEMI) is the same as

Parenteral anticoagulant: o

UFH, enoxaparin, or fondaparinux for 48 hours. Fondaparinux is especially useful if there is risk

ASA with either clopidogrel or ticagrelor. Always give dual antiplatelet therapy.

5-5). Also know that STEMI includes those with

in V1, V2). General measures are discussed above.

Antiplatelet therapy: o

(Figure

a posterior infarct (ST depression in V 1, V2 and tall Rs

of bleeding. •

for those with a new left bundle-branch block (LBBB)

The following are additions to the general measures for all ACS patients discussed on page 5-18.

Prasugrel or lib/Ilia inhibitors are not given for

STEMI (or new LBBB) patients get the following

conservative therapy.

medical therapy:

This is basically the same anticoagulant/antiplatelet

•

treatment as those getting UA/NSTEMI early invasive

Parenteral anticoagulant: o

(which ideally should be nearly everybody).

not used and fondaparinux is now a reasonable option. Again, remember that UA/NSTEMI patients do not receive fb i rinolytic therapy.

Long-Term Antiplatelet Therapy after UA/ NSTEMI Without a stent:

UFH, enoxaparin, or bivalirudin. Give UFH or bivalirudin if going to cath lab within 24 hours

therapy, except that lib/Ilia inhibitors and prasugrel are •

Antiplatelet therapy: o

ASA plus clopidogrel, prasugrel, or ticagrelor

IIb!IIIa inhibitors as early as possible when

(in emergency department) patients are going to the cath lab for PCI

Immediate Reperfusion Therapies

•

ASA 75�162 mg/d for life

Overview

•

Clopidogrel or ticagrelor x I month to 1 year

Consider

emergent

reperfusion

(primary

PCI

fibrinolytic therapy) in all patients who present within 12 hours of the onset of symptoms with a STEMI or a new (or presumed new) LBBB.

ACUTE CORONARY SYNDROME

uiz •

What are the reperfusion therapies you give to (or consider for) those with STEMI or new LBBB? Who gets what?

•

In what conditions has PCI been shown to be better than fibrinolytic therapy?

•

In what conditions has PCI been shown to be especially indicated?

•

What are the absolute and relative

Primary PCI is particularly beneficial in patients with highest risk for mortality (e.g., cardiogenic shock) or acute severe HF following a STEMI or new LBBB MI.

contraindications to fibrinolytic therapy? Primary PCI

Primary percutaneous coronary intervention (PCI) is urgent reperfusion therapy typically using a stent (bare-metal or drug-eluting). BMSs should be used in patients with high bleeding risk, inability to comply with I year of dual antiplatelet therapy, or anticipated inva sive or surgical procedures in the next year (Image 5-6). Primary PCI has been shown to be superior to fibrinolytic therapy when used in patients with STEM!, MI with new LBBB, and new true posterior MI. Outcomes are also better than fibrinolytic therapy as long as an experienced practitioner performs the procedure without signifi cant delay, particularly within 12 hours of the onset of symptoms-and within 90 minutes of the arrival of the patient in the emergency department. (Door-to-balloon time is a commonly measured metric for quality of care in STEM!.) Patients with STEM! who present to a hospital without PCI capabilities should be trans ferred to a PCI-capable hospital with a goal of no more than 120 minutes from first medical contact (FMC) to stent placement.

STEMI or new •

Give aspirin,

LBBB Ml: 02 prn, beta-blocker,

nitrate prn.

·Give UFH, enoxaparin, or bivalirudin. • • •

Give clopidogrel, prasugrel, or ticagrelor. Abciximab (GP lib/lila) only if immediate PC I. Monitor for rhythm and ischemia.

Percutaneous coronary intervention (PCI)

Fibrinolytic therapy if not contraindicated and if PCI not immediately available

PCI should be done within within

Image 5-6: Angiogram of a blocked coronary arte1y before and after stent placement

In the patient who presents with completed STEM! (beyond 12 hours of the onset of symptoms), coronary angiogram is indicated if the patient continues to have chest pain or is in heart failure, left ventricular ejection fraction (LVEF) is moderately to severely reduced, there is electrical instability (ventricular tachycardia [VT] or ventricular fibrillation [VF]), or post Ml stress test shows significant ischemia. Fibrinolytic Therapy

If reperfusion therapy is indicated and primary PCI is not available at the first hospital, or FMC-to-device time at a PCI-capable hospital exceeds 120 minutes, initiate fibrinolytic therapy in STEM! patients in the absence of contraindications. Many studies show that the sooner the patient receives fibrinolytic therapy, the greater the benefit in reduction of mortality, with the most benefit in the first 4 hours and the greatest of all in the first hour. Patients with new bun dle-branch block benefit the most, followed by anterior Ml, then inferior MI. Start fibrinolytic therapy within 30 minutes of arrival in the emergency department. Note: Fibrinolytics are used for patients at facilities that do not have the capabilities for urgent PCI. Following treatment with fibrinolytic therapy, high-risk STEMI patients (recurrent ischemia, cardiogenic shock, severe HF, or other high-risk features) should be transferred to a PC! center to undergo coronary angiography and PCI immediately-without waiting to determine whether reperfusion has occurred. Fibrinolytic agents include the recombinant, tissue-type plasminogen activators (e.g., rt-PA, TNK), anistreplase, streptokinase, and urokinase. Contraindications to fibrinolytic therapy can be either absolute or relative contraindications. Absolute contraindications:

hrs of chest pain onset and

90 min of

arrival to emergency department

F igure 5-5: Acute Ml Treatment Pathway with STEMI or New LBBB

•

MedStudy

Previous hemorrhagic stroke at any time; other cerebrovascular events within I year Intracranial neoplasm Active internal bleeding Suspected aortic dissection

5-21

5-22

ACUTE CORONARY SYNDROME

Relative contraindications: •

•

Persistent BP

Complications of Myocardial Infarction

> 180/110

Left Ventricular Dysfunction

Remote nonhemorrhagic CVA (>

I year)

Left ventricular dysfunction after an MI is predictive

Current use of anticoagulants with INR > 2-3;

bleeding diathesis

poor

prognosis.

Pump

failure

now

the

primary cause of in-hospital death from ST eleva

Recent (2-4 weeks) major trauma or surgical

tion MI (STEMI). Patients in cardiogenic shock have

procedure

historically had mortality rates of

•

Noncompressible vascular puncture

using PCI or emergent CABG have demonstrated an

•

Previous exposure to streptokinase/anistreplase

improvement in these dismal outcomes.

•

Pregnancy

•

Active peptic ulcer

•

> 85%, but studies

Right Ventricular Infarction Complications

Of the patients with STEMI!new LBBB initially eval uated for fibrinolytic therapy, almost 2/3 do not get fibrinolytic therapy for the reasons listed above or because of advanced age. The risk of intracranial hemor

Right

ventricular

infarction

(RVI)

frequently

accompanies an inferior Ml and is almost always due to occlusion of the proximal right coronary artery. Inferior MI complicated by RVI has a significantly

rhage increases with age, to as much as 1% in patients

worse prognosis than inferior MI alone.

> 75, but age by itself is no longer a contraindication.

ST-segment elevation in right-sided chest leads (e.g.,

Many of these patients are still good candidates for primary PCI.

V3R- V7R) is an indication of infarction of the right ventricle. If a patient with inferior MI presents with hypotension, suspect RVI.

Additional Recommendations from the

Suspect RVI in all cases of inferior Ml, which is

2013 ACC I AHA STEM! Guidelines

typified by the clinical triad of hypotension, clear lung fields, and elevated jugular venous pressure. A

•

Stop all NSAIDs (except ASA), including COX-2s!

•

Start oral beta-blocker within 24 hours if no signs of

If you perform right heart catheterization, an elevated

HF, evidence of low-output state, increased risk for

RA pressure of 2: 10 mmHg with decreased pulmonary

cardiogenic shock, PR interval > 0.24 seconds, 2"ct

•

Kussmaul sign is frequently present.

or 3'ct degree heart block, active asthma, or reactive

capillary wedge pressure (PCWP) and CO are quite

airway disease.

specific for right ventricular MI.

Do not give fibrinolytic therapy if immediate PC! is

Management

anticipated. ln addition, there is no role for partial- or

RVI

frequently

diametrically

opposed to that of LV infarction. Avoid nitrates and

low-dose fibrinolytic therapy.

preload reducing agents. Fluid support is essential.

•

Give clopidogrel or ticagrelor (no PCI) + ASA

Inotropic support, typically with dobutamine, may

(I year).

be necessary.

•

Place patient on a high-dose statin.

•

ACEis within 24 hours to all with anterior STEM!,

Arrhythmias and Blocks

HF, EF :S 40% (unless contraindicated). Use an

A variety of tachyarrhythmias can occur with myocardial

angiotensin receptor blocker if ACE! intolerant. •

infarction/ischemia.

An aldosterone antagonist (e.g., spironolactone,

Atrial fibrillation (A-fib) with hemodynamic instability

eplerenone) should be given to those with no contraindications who are already receiving an ACEI and beta-blocker, have an EF :S 40%, and have either symptomatic heart failure or diabetes mellitus. •

•

IV nitroglycerin in the first 24 hours for ongoing chest

synchronized cardioversion. If patients do not require cardioversion, control the ventricular rate in these patients with beta-blockers, diltiazem, or digoxin.

pain or hypertension.

Treat

Blood sugars must be maintained at

ventricular tachycardia (VT) with defibrillation (DC

180 using

hypoglycemia.

For

Influenza vaccine yearly.

and

clopidogrel,

prasugrel,

and/or

ticagrelor

should be stopped 24 hours before urgent on-pump antagonists

(eptifibatide,

tirofiban)

should

discontinued at least 2-4 hours before urgent CABG; abciximab should be discontinued at least 12 hours before urgent CABG.

(VF)

and

pulseless

sustained

with

pulse

accompanied

cardioversion. For episodes of sustained

VT not associated with

hemodynamic instability:

CABG. Short-acting intravenous GP lib/Ilia recep tor

fibrillation

hemodynamic instability, treat with DC synchronized

If urgent CABG is planned, aspmn should be with held,

ventricular

unsynchronized cardioversion).

insulin-based regimens for diabetics while avoiding

•

requires emergent treatment with direct current (DC)

•

Amiodarone is the drug of choice. It can be given as a continuous infusion or as boluses every l 0-15 min utes. Lidocaine can be an effective alternative agent, and procainamide is also an option.

ACUTE CORONARY SYNDROME

Mechanical Complications after STEM I

Rupture of a papillary muscle, if it occurs, usually does so •

How does management of RVI differ from

may (or may not) hear a short, early systolic murmur.

LV infarction? •

Echocardiography is indicated in any hemodynami cally unstable MI patient and is the diagnostic modality

Which patients with VT after an Ml get DC

of choice for all of these conditions. The treatment is

cardioversion? •

urgent cardiothoracic surgery.

What are the medical options for

Ventricular septal defect, if it occurs, generally does so

hemodynamically stable Ml patients with VT? •

3-7 days after an anteroseptal MI. Incidence is about 0.3% of Mls (before reperfusion therapy era, incidence was 1-3%). Again, the patient rapidly develops shock.

When do the major mechanical complications tend to occur after an Ml? How do they present? What is the best initial test to diagnose such a

A loud, holosystolic murmur is heard widely over the

complication? •

3-7 days after an inferior MI. The patient rap

idly develops shock and acute pulmonary edema. You

G R

precordium. Samples from a right heart catheter dem

When should a patient with STEM I be referred

onstrate an oxygen saturation step-up from the right

for consideration for an lCD?

atrium to the pulmonary artery of at least

10%. Confirm

the diagnosis by echocardiography. Once again, the

V d ti e n U

•

Correct any hypokalemia or hypomagnesemia.

mortality rate is very high, and the only treatment is

•

Routine prophylactic use of lidocaine to prevent VT

urgent cardiothoracic surgery.

is no longer recommended. For

patients

who

F ree-wall rupture of the LV commonly occurs

develop

ventricular

or ventricular fibrillation after the first

tachycardia

48 hours, the

short-term and long-term mortality rates are increased. Such patients should be considered for electrophysiologic study and an implantable cardioverter-defibrillator (lCD). Note that patients with isolated, premature ventricular contractions, or runs of nonsustained

(< 30 seconds)

VT, do not need antiarrhythmic therapy on a routine

basis. Beta-blockers are effective for ventricular ectopic activity and preventing arrhythmias.

9 ri 9

Bradycardia and AV block are more common with

inferior Mls than anterior Mls because of the increased vagal tone and AV nodal ischemia associated with an

inferior infarct. Remember: Prognosis is related to the size of the infarct, not the presence of AV block itself. The block is often transient and does not require a permanent pacemaker. AV

block

h ta

accompanying

implies

destruction of a large amount of myocardium in the interventricular

septum,

is associated

with

high

mortality, and frequently requires permanent pacing if the patient survives.

Indications for temporary pacing at the time of an MI include: •

Symptomatic bradyarrhythmias unresponsive to medical treatment

•

Asystole or sinus arrest

(3rd degree) AV block Mobitz type 2 second-degree AV block Complete

3-7 days

after a large, anterior MI, most frequently in elderly hypertensive women. Sudden syncope is typical. The neck veins are grossly engorged from tamponade; pulsus paradoxus, tachycardia, and hypotension make up the triad. Hemodynamic collapse occurs quickly. There have been a few heroic saves with immediate surgery, but rapid death is the usual outcome. The

2013 ACC/AHA STEMI guidelines recommend

diagnosis of mechanical complications after STEMI with transthoracic echocardiography. Arterial pressure monitoring with an indwelling arterial line is appropriate in some patients, particularly those requiring mechanical ventilation. Intraaortic balloon counterpulsation is indi cated in patients in cardiogenic shock after STEMI who do not quickly stabilize with pharmacological therapy or with a mechanical complication as a bridge to urgent revascularization and/or surgery.

Implantable Cardioverter-Defibrillators Implantable

cardioverter-defibrillator

(ICD)

therapy

is indicated before discharge in patients who develop sustained

ventricular

tion more than

tachycardia/ventricular

fibrilla

48 hours after STEMI, provided the

arrhythmia is not due to transient or reversible ischemia, reinfarction, or metabolic abnormalities. Studies have shown that ICDs prolong survival in post-MI patients with LVEF

30-35%, depending on

NYHA classification. LVEF is typically reevaluated after

40 days following revascularization to allow stunned or hibernating myocardium to recover. An ICD is particu larly indicated if there are baseline episodes of ventricular tachycardia.

5-23

5-24

CORONARY ARTERY DISEASE

Patients in the above 4 groups should receive a statin

CORONARY ARTERY DISEASE

medication.

NOTE

Lipids can be falsely low for up to 2 months after a

We'll talk about the risk factors for coronary artery disease(CAD), screening, and revascularization options.

myocardial infarction or cardiac surgery. Statins

enhance

plaque

stabilization

and

can

independently improve long-term prognosis. ACCIAHA guidelines and drug treatment are covered in

RISK FACTORS FOR CAD

Endocrinology, Book 4, under Lipoproteins.

The primary risk factors for CAD:

Additional factors to consider:

•Age

•Advise no smoking.

•Male gender

•Give antihypertensive medications to treat to goal BP.

•Family history of early CAD(females< 65,

•Coronary artery calcium scores and other serum

males< 55)

G R

markers, such as high-sensitivity CRP, can be used

•Smoking

in some patient populations to add to the total risk

•Hypertension

assessment for coronary artery disease.

•DM

•Do not forget to ask about substance abuse,

•Elevated LDL level

particularly cocaine.

V d ti e

Aerobic exercise and elevated HDL are inversely linked to CAD. HDL is increased by exercise, estrogens, niacin, and small amounts of EtOH. HDL is decreased by smoking and androgens. However, pharmacologic

REVASCULARIZATION

The revascularization options are:

treatment of low HDL is no longer recommended by

•Coronary artery bypass graft(CABG)

national guidelines.

•Percutaneous coronary intervention(PC!) with either stents or angioplasty

SCREENING

n U -

CABGvs. PCI

Check a "fasting lipid panel" at least every 5 years in

healthy persons, starting at age 20 . The "fasting lipid panel" includes total cholesterol, LDL, HDL,

and

triglycerides. Much more on lipids in Endocrinology, Book 4!

9 9

LDL is usually a calculated value:

r i h

Cholesterol

Reduce

ACC/AHA

guidelines

recommend

•CABG to improve survival for all patients with significant, left main CAD(> 50% diameter stenosis).

20 13 ACC/AHA Guideline on the Treatment Blood

2012

•CABG to improve survival in patients with significant

LDL =total cholesterol- HDL- l/5 of triglycerides The

The

revascularization under the following circumstances:

Atherosclerotic

(> 70% diameter) stenoses in 3 major coronary arter ies or in the proximal LAD artery plus I other major

coronary artery(e.g., proximal circumflex).

•CABG is reasonable to improve survival in patients

Cardiovascular Risk in Adults states that all patients

with significant(> 70% diameter) stenoses in 2 major

with CAD should receive a high-intensity statin, regard

coronary arteries with severe or extensive myocar

less of lipid levels. (A high-intensity statin is defined

dial ischemia(i.e., high-risk criteria on stress testing,

as one that lowers LDL cholesterol by at least 50% on

abnormal intracoronary hemodynamic evaluation,

average. Currently, that includes atorvastatin 40-80 mg

or > 20% perfusion defect by myocardial perfusion

and rosuvastatin 20-40 mg. A moderate-intensity statin

stress imaging) or target vessels supplying a large

is one that lowers LDL cholesterol by 30 to< 50%. That

area of viable myocardium.

includes all other available statins plus the lower doses of atorvastatin and rosuvastatin.)

with mild-to-moderate left ventricle(LV) systolic

The 2013 ACC/AHA guidelines identify 4 statin benefit groups:

I) Patients with clinical atherosclerotic cardiovascular disease(ASC VD)-such as CAD or stroke

dysfunction(EF 35-50%) and significant(> 70% diameter stenosis) multivessel CAD or proximal LAD coronary artery stenosis, when viable myo cardium is present in the region of intended revascularization.

2) Patients with LDL � 190 mg/dL

•CABG is recommended to improve survival in

3) Patients ages 40-75 with OM and LDL 70-189 mg/dL 4) Patients without clinical ASCYD or DM who are ages 40-75 with LDL 70-189 mg/dL and an estimated 10-year ASCYD risk of 7.5% or higher

•CABG is reasonable to improve survival in patients

patients with complex 3-vessel CAD with suitable anatomy and in those with multivessel CAD and dia betes mellitus, particularly if a left internal mammary artery graft can be anastomosed to the LAD artery.

CORONARY ARTERY DISEASE

patient populations and coronary lesions that benefit from CABG vs. PCI, particularly in the drug-eluting stent era. This is a "moving target" because left main disease can be stented as well now with good results in •

What are the primary risk factors for CAD?

•

What increases HDL?

•

certain patient groups. Again: Survival does not improve after bypass unless the patient has:

Which patient groups definitely should get CABG?

•

Which patient groups could get either PCI

•

or CABG? •

•

In 3-vessel disease, what is the benefit of

left main or left main-equivalent disease, or diabetes.

CABG-survival, symptoms, or both?

Stents

With saphenous vein bypass, what percentage

Stents are the mainstay ofPCI. These are placed in the area

G R

of blockage and then expanded, thereby opening the lumen

of veins is occluded in 10 years? •

3-vessel disease with significant LV dysfunction, or

to normal size. Stents do not cause as much dissection of

Name 2 drugs used with DESs.

the plaque and are not susceptible to elastic recoil-both of which can occur with angioplasty alone. Stents also have a

•

PCI or CABG to improve symptoms is beneficial in patients with l or more significant

(> 70%

restenosis is almost always due to neointimal hyperplasia,

diameter) coronary artery stenoses amenable to

•

but stents also carry a risk of in-stent thrombosis, particu

revascularization and unacceptable angina despite

larly during the early period after placement. This is why

optimal medical therapy.

antiplatelet therapy is so important after stent placement,

PCI or CABG to improve survival for survivors of

and a bare metal stent requires dual antiplatelet therapy

sudden cardiac arrest with presumed ischemia-medi

for a minimum of30 days to prevent in-stent thrombosis.

ated ventricular tachycardia caused by significant

Drug-eluting stents (DESs) are made with a metallic

(> 70% diameter) stenosis in a major coronary artery. •

stent backbone supporting a polymer covering that con

PCI is reasonable as an alternative to CABG in selected stable patients with significant

tains a slow-release drug. These drugs have properties

(> 50%

diameter stenosis) unprotected left main CAD with anatomy associated with a low risk ofPCI complica tions and a good, long-term outcome, and clinical characteristics predicting a significantly increased

9 9

surgical morbidity/mortality.

CABG improves symptoms and survival in: •

Left main, left main-equivalent (2-vessel disease with

that decrease the neointimal hyperplasia that is the cause

I vessel being proximal LAD), or 3-major coronary

h a

artery disease •

Multivessel CAD or proximal LAD disease with LV dysfunction and viable myocardium

•

V d ti e n U

lower restenosis rate than plain angioplasty. The in-stent

Complex 3-vessel CAD

Multivessel CAD with DM

With saphenous vein bypass, there is a 50% chance of occlusion in I 0 years (about 5% per year), but with internal mammary grafts, 90% are open at 10 years! Think: the word " VEINS" has 5 letters and so 50% open at I 0 yrs; "LIM-ARTERY" has 9 letters so 90% open at

I 0 years! Internal mammary grafts are the standard of care for surgical revascularization of the LAD. Chance of MI is the same after bypass. CABG vs. PCI: In most of the recent trials, patients have the same survival results, but the need for revas cularization is greater in the PCI group. In these trials, survival has been better for diabetics who get an inter nal mammary-LAD bypass than for those with a PCI. Studies are continually trying to tease out specific

MedStudy

of most restenoses. Commonly used DESs contain med ications such as sirolimus, paclitaxel, and everolimus. With these agents, the restenosis rate drops dramati cally (to 5%) compared to bare-metal stents ([BMSs]; 25%), although there is a slight increase in late stent thrombosis (0.4%). As opposed to BMSs, DESs require prolonged obligatory dual-antiplatelet therapy due to the delay in neointimalization: minimum I year as opposed to30 days with a BMS. There are growing concerns over late stent thrombosis with DES, particularly after anti platelet agent withdrawal. Also, rare local and systemic hypersensitivity reactions have been reported and can contribute to late stent thrombosis risk. Thus, prolonged antiplatelet therapy may be needed >

I year.

Other Balloon angioplasty stretches the plaque and vessel wall to enlarge the lumen. There is a 30-50% chance of reste nosis within 6 months. Balloon angioplasty is currently used for vessels too small to allow coronary stenting. It is also used to predilate vessels before stent placement. Rotational

ablation

atherectomy

(catheter

with

diamond-grinding chips in it) has a role for heavily calcified lesions.

5-25

5-26

PERIPHERAL ARTERIAL DISEASE

Magnetic

P ERIPHERAL ARTERIAL DISEASE

resonance

angiography

(MRA)

the

extremities (with gadolinium enhancement) is useful to diagnose anatomic location and degree of stenosis of

CAUSES OF PAD AND

PAD. Computed tomographic angiography (CTA) can be

INTERMITTENT CLAUDICATION

considered as a substitute if there are contraindications

P eripheral arterial disease (PAD), previously called

to MRA.

peripheral vascular disease (P V D), has many causes,

Contrast angiography provides detailed information

including the following: •

about

and

recommended

for

common cause in middle-aged and older); 2 major risk

revascularization is contemplated.

factors for arteriosclerotic PAD are diabetes (5x greater

Thromboembolism is the usual problem with aneurysms

include hyperhomocysteinemia, hyperlipidemia, and hypertension. Note: Patients with arteriosclerotic PAD are at increased risk of MI and stroke.

of limb arteries. Aneurysm of the popliteal artery can be diagnosed by U/S or CT scan. In patients with femoral

G R

or popliteal aneurysms, U/S (or computed tomography or magnetic resonance) imaging is recommended to

Arteritis (connective tissue disease, Takayasu

exclude contralateral femoral or popliteal aneurysms

arteritis).

and abdominal aortic aneurysms (AAAs).

•

Trauma (jackhammer hands).

•

Buerger disease (especially smoking males< 30 years old}-also called thromboangiitis obliterans. It involves medium and small arteries and often affects arteries of the wrists (positive Allen test) and hands.

•

anatomy

evaluation of patients with lower extremity PAD when

chance) and smoking. Other modifiable risk factors

•

arterial

Arteriosclerosis (arteriosclerosis obliterans-most

Entrapment-think especially of thoracic outlet

Recommendations: •

Statin in all patients.

•

Keep BP < 140/90 or< 130/80 with DM or CKD;

syndrome and popliteal artery entrapment. Suspect popliteal artery entrapment in young men with

beta-blockers are effective and not contraindicated. •

Proper foot care.

•

Smoking: Counsel to stop smoking, offer behavioral

n U -

intermittent claudication of calf or foot arch with walking-but not running!

V d ti e

TREATMENT OF PAD

and pharmacologic Rx (varenicline, bupropion, and

nicotine replacement therapy); ask smokers/former

It is important to differentiate vascular claudication from

smokers about tobacco use at every visit.

lumbar spinal stenosis, and know that the latter causes a pseudoclaudication. L umbar spinal stenosis is relieved

•

Antiplatelet therapy with aspirin 75-325 mg or clopi

only by sitting down (flexing the spine), but not by

dogrel 75 mg daily is indicated as well to decrease

standing still. It is exacerbated by anything that extends

cardiovascular events (warfarin gives no benefit!).

9 9

the spine, such as standing or walking (especially down

hill). Vascular claudication is relieved by sitting down or standing still. Neither disease causes nocturnal leg

r i h

•

Exercise 30-45 minutes at least 3 days/week.

•

Cilostazol (Pletal®) 100 mg bid, a phosphodiesterase inhibitor that increases the cAMP in platelets and

cramps. When the distance to onset of claudication or

blood vessels-resulting in a reversible inhibition

severity abruptly changes, thrombosis in situ or an

of platelet aggregation-has been shown to improve

embolic event should be considered.

DIAGNOSIS OF PAD

symptoms and increase walking distance. Use only if LV function is normal because patients with class III or IV heart failure have increased mortality with any phosphodiesterase inhibitor.

The resting ankle brachial index (ABI) should be used to establish the lower extremity PAD diagnosis in patients

•

P entoxitylline (Trental®) effect is marginal and not well established.

with suspected lower extremity PAD; i.e., those with 1 or more of the following: exertional leg symptoms, non

If PAD is due to Buerger disease, stop tobacco use.

healing wounds, age 2: 65, or 2: 50 years if history of

smoking/diabetes.

with steroids.

ABI classification: noncompressible

Takayasu

arteritis

present,

treat

the

disease

1.40, normal

Other treatment: Many forms of PAD can now be

1.00-1.40, borderline 0.91--0.99, and abnormal (i.e.,

effectively treated with percutaneous intervention (angio

PAD)< 0.90.

plasty and stents}-with low restenosis rates. Surgical

Continuous-wave Doppler ultrasound is useful to diagnose anatomic location and degree of stenosis of PAD. Exercise tolerance tests (ETTs) are recommended to objectively measure functional limitation of claudica tion and response to therapy. ETTs with pre-exercise and post-exercise ABI values provide diagnostic data useful in differentiating arterial claudication from nonarterial

bypass can also effectively relieve symptoms and isch emia. In general, proximal (iliac and femoropopliteal) stenosis and short-segment occlusions are best treated endovascularly (e.g., focal aortoiliac occlusive disease), with long lesions and occlusions best treated surgically. With acute peripheral arterial occlusion, heparin protects the collateral circulation during evaluation by preventing

claudication ("pseudoclaudication").

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VASOSPASTIC DISEASE

•

What are the causes of arteriosclerotic PAD?

•

What is Buerger disease?

•

What is the difference between claudication and pseudoclaudication?

•

What is the first test to establish the diagnosis of lower extremity PAD? What result is considered abnormal?

•

What antiplatelet therapy is recommended for patients with PAD?

•

G R

Image 5-7: Thromboangiitis obliterans or Buerger disease

What is primary Raynaud syndrome? How is it

symptoms on patients toes

treated? •

In asymptomatic patients with known or suspected

Atherosclerotic disease of the carotid artery

carotid stenosis, ultrasound is recommended as the initial

provides more risk for which of these: Ml,

•

carotid stenosis.

When is carotid endarterectomy indicated?

Ultrasound is also recommended to detect carotid stenosis

thrombus formation around the new clot. Many arterial emboli to the lower extremities come from the heart, but atheromatous emboli from a diseased aorta can also occur, which can cause renal failure and ischemia of the toes (Image

V d ti e n U

diagnostic test to detect hemodynamically significant

stroke, or TIA?

5-7). Embolectomy/thrombectomy is the

treatment of choice.

in symptomatic patients (i.e., who develop focal neuro logical symptoms in left or right internal carotid artery territories). Magnetic resonance angiography (MRA) or computed tomography angiography (CTA) is indicated to detect carotid stenosis when ultrasound cannot be obtained or yields equivocaVnondiagnostic results. Patients who experience nondisabling ischemic stroke or

VASOSPASTIC DISEASE

Vasospastic disorders: Primary Raynaud phenomenon

9 ri 9

(Raynaud disease) is constriction of small arteries and

TIA symptoms within 6 months (symptomatic patients) should undergo carotid endarterectomy (CEA) if:

1) the

diameter of the lumen of the ipsilateral internal carotid artery is reduced

(> 70% by noninvasive imaging or > 50% by catheter angiography); and 2) the anticipated

arterioles when cold, leading to acrocyanosis. It is some

rate of perioperative stroke/mortality is

times associated with livedo reticularis. It involves small

artery stenting is indicated as an alternative to CEA for

arteries and arterioles in the digits and skin (Image

5-8).

Treatment: calcium channel blockers (CCBs), biofeed

h ta

back, and nitroglycerin if CCBs are ineffective.

Prinzmetal angina is a coronary artery vasospastic disease that can lead to transient, dramatic ST elevation mainly at rest and occasionally with exercise. T hink of this diagnosis in a younger individual with transient ST elevation during an episode of pain but normal coro nary arteries on cath. Treatment includes nitrates and

6%. Carotid

these same patients. It has the same indications as CEA but stenting has a higher 30 day postsurgical mortality, so it typically is used for a subset of these patients with a lesion not suitable for surgery, restenosis after previous CEA, or radiation stenosis. Medical therapy for atherosclerotic includes:

aspirin,

clopidogrel,

carotid disease

low-dose

aspirin

+extended release dipyridamole; treat blood pressure to goal

140/90; statins for all; and smokers should quit!

especially calcium channel blockers.

CAROTID ARTERY DISEASE CAROTID ARTERY ATHEROSCLEROSIS Atherosclerosis within the carotid artery occurs most frequently within the common carotid bifurcation and proximal internal carotid artery. Patients with athero sclerotic carotid artery disease are at a higher risk of having an MI than of having a transient ischemic attack (TIA) or stroke! Image 5-8: Acute Raynaud phenomenon

5-27

5-28

CEREBRAL EMBOLIC DISEASE

INTERNAL CAROTID ARTERY

AORTIC DISEASE

DISSECTION Suspect spontaneous dissection of the internal carotid

AORTIC ANEURYSMS

artery (cervical area) in a patient with unilateral head

Overview

ache associated with either TIAs or a dilated pupil. It can also present with only a history of unilateral neck pain in a hypertensive patient. Look for cholesterol emboli on the funduscopic exam. Spontaneous dissec tion of the internal carotid artery typically resolves with no treatment, with excellent recovery. Occasionally, anticoagulation or a stent is needed.

The

causes

categorized

of as

developmental

aortic

aneurysms

degenerative diseases,

can

diseases,

infections,

broadly

inherited

vasculitis,

or and

trauma. With aortic aneurysms, rupture is the biggest threat. Atheroembolism

another

complication

abdominal aortic aneurysm. Signs of atheroembolism, in decreasing order, are: livedo reticularis, then blue toes, then ischemic ulceration. (Remember, though, that most emboli to the lower extremities originate in the heart!)

CEREBRAL EMBOLIC DISEASE

G R

Hypertension from progressive renal insufficiency can occur if abdominal aneurysms are not treated.

OVERVIEW The causes of cerebral embolic events of cardiac origin (and the approximate % of events they cause): •

Atrial fibrillation (45%)

•

Acute MI (15%)

Thoracic Aortic Aneurysms

V d ti e

Thoracic aortic aneurysms tend to dissect as well as rupture. Aortic dissection is an intimal tear in the aorta, resulting in a dissecting hematoma, which can cause severe

•

Ventricular aneurysm (10%)

•

Mechanical valve prosthesis (10%)

•

Valvular heart diseases, including endocarditis ( 10%)

•

Other cardiac abnormalities (1 0%)

pain and occlusion of the aorta and involved vessels. Systemic hypertension, cystic medial necrosis, bicuspid aortic valve, coarctation of the aorta, and 3rd trimester of pregnancy are predisposing factors. Aortic dissection is a

n U -

"Other" includes patent foramen ovale, which allows an

major cause of death in those with Marfan syndrome.

intermittent right-to-left shunt and "paradoxical" emboli,

Cystic medial necrosis is the most common pathology in

and dilated cardiomyopathy, which allows formation of

ascending aortic aneurysms, whereas atherosclerosis is

a mural thrombus.

most frequently associated with aneurysms of the aortic

Noncardiac

cause

embolic

cerebral

events

atherosclerosis, both aortic and carotid (discussed above).

9 9

Nonembolic causes of cerebral ischemic attacks or strokes are thrombosis, systemic hypoperfusion, and blood disorders (especially clotting disorders).

definition

r i h

transient

ischemic

attack

The DeBakey classification of aortic dissection lists 3 types:

Type 1: Involves the ascending aorta, aortic arch, and descending aorta

Type II: Proximal in the ascending aorta alone

TRANSIENT ISCHEMIC ATTACK The

arch and descending thoracic aorta. The average growth

rate of thoracic aneurysms is 0.1-0.2 em per year.

(TIA)

Type Ill: Involves the descending aorta alone, commonly

has changed and is no longer related to duration of

just after the subclavian artery

symptoms. TIA is now defined as any period of CNS

The Stanford classification lists 2 types:

ischemia without infarction. Ischemic stroke is defined as ischemia with infarction. The CNS includes the brain, spinal cord, and retina. More on TIA under Dizziness, Causes of Vertigo in Neurology, Book 5.

Type A: Any dissection involving the ascending aorta Type B: Limited to the descending aorta only Stanford Type A combines DeBakey I and II; this makes

Medical treatment of TIA: If there is a history of TIA

sense because all type A aortic dissections are managed

but no history of cardioembolic stroke, no significant

similarly. Hence, the Stanford classification is more

lesion is found, and the patient does not have atrial fibril

commonly used now.

lation, it is probable that the cause is atherosclerosis; therefore, the patient should be placed on antiplatelet therapy: ASA + dipyridamole, ASA alone, or clopidogrel alone. Ticlopidine is similar to clopidogrel but is not a I 51 line drug because of severe neutropenia that occurs in

1%! Unlike with coronary artery disease, the combination of ASA + clopidogrel has not been shown to be beneficial over either agent alone for stroke or TIA prevention.

Proximal

dissection can cause aortic

hemopericardium with

regurgitation,

tamponade, and MI due to

involvement of a coronary artery (usually the right coro nary artery). Dissections typically present with severe anterior chest pain and/or severe interscapular pain. Diagnosis [Know]: CT and MRI are the diagnostic procedures of choice for possible aortic dissection. Transesophageal echo is a reasonable alternative if the patient is too unstable to go to radiology.

VALVULAR HEART DISEASE

stress test if the patient has 2': 2 CAD risk factors (listed

. Jrl.... Q..,_.-·quiZ .

•

on page 5-24 ).

•

or common iliac aneurysms are options in good surgi cal candidates; however, endovascular repair requires

its prognosis?

•

periodic long-term surveillance imaging to monitor

What are the procedures of choice for

endoleak, shrinkage/stability of excluded aneurysm sac,

diagnosing a dissecting aortic aneurysm?

and to determine need for further intervention.

At what size is surgery indicated for a thoracic aortic aneurysm?

COARCTATION OF THE AORTA

At what size is surgery indicated for an

Coarctation of the aorta (COA) is a congenital problem

abdominal aortic aneurysm? •

Open or endovascular repair of infrarenal AAAs and/

How might spontaneous dissection of the internal carotid artery present clinically? What is

•

Use perioperative beta-blockers

patients with CAD undergoing surgical repair of AAA.

that causes persistent hypertension, sometimes even after

G R

Which Streptococcus, if found as a cause of

surgical correction. Cardiac output responds normally to

endocarditis, warrants a colonoscopy?

exercise. Blood pressure is higher in the upper extremi ties than in the lower. People with COA have a high risk

Treatment:

Decrease

elevated

blood

pressure

immediately with beta-blockers and nitroprusside. There is preliminary evidence that Marfan's-related aneurysms should be treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) to block TGF-signaling. Ascending aortic dissec tions are at greater risk for complications, so they always require

surgery. Descending

aortic

dissections

are

mainly treated medically unless evidence of end-organ damage develops (renal insufficiency, GI ischemia, limb compromise), which suggests continuing dissection and the need for emergent surgery. Thoracic aortic aneurysm: Surgery is indicated at 5.5 em

in the ascending aorta (5 em ifMarfan's) and 6 em in the descending aorta.

of developing subsequent aortic disease, including aneu rysms and dissection, even after correction of the lesion.

V d ti e n U

A bicuspid aortic valve is often seen

INFECTIVE END OCARDITIS Overview

[Know this section well.]

More on causes and treatments of infective endocarditis (IE) is discussed in Infectious Disease, Book 1. For treatment purposes, endocarditis is classified as: Native valve

Prosthetic valve

symptoms, compressing surrounding structures, or is of

•

IV drug related

traumatic origin.

•

Culture negative

9 ri 9

h ta

Abdominal Aortic Aneurysm

50%) in COA

VALVULAR HEART DISEASE

•

enlarging rapidly (> I 0 mm in a year), associated with

�

patients. See more on COA on page 5-58.

•

Also, surgery is indicated if the aneurysm is small but

(

These can have acute or subacute presentations.

Screening is covered in General Internal Medicine, Book 5, under Preventive Medicine, Screening Exams. Abdominal aortic aneurysms (AAAs) are more common in men. They tend to rupture rather than dissect. Treat

Streptococcus, Enterococcus, and S. epidermidis are the usual causes of the subacute form, while S. aureus, group B Streptococcus, and gram-negative organisms cause acute endocarditis.

S. aureus causes 80-90% of staphylococcal IE and is the

BP and lipids as for patients with CAD, and advise to

most common cause of acute IE. Recent data from the

stop smoking

International Collaboration on Endocarditis (ICE) sug

(and

interventions). If

asymptomatic,

recommend

aneurysms

smoking

4--5.4

cessation

gest that S. aureus has become the leading cause of IE em

should

monitored with ultrasound or CT every 6--12 months.

worldwide in injection drug users and prosthetic valves and most often presents as an acute disease.

Aneurysms > 5.5 em or symptomatic (abdominal/back

Strep accounts for 60-80% of all endocarditis cases.

pain + pulsatile mass + hypotension) should undergo

Viridans streptococci are responsible for 30-65% of

surgical repair. AAAs that expand > 0.5 em in 6 months

native valve endocarditis in adults. S. bovis is often

should undergo surgical repair as well. Put the patient on

associated with a GI malignancy in the elderly as well

beta-blockers during the observation period.

as polyps and diverticulosis--order colonoscopy in all

Know that acute MI and other CAD-related problems

patients with S. bovis endocarditis.

are the cause of70% of perioperative mortality for AAA

Enterococcal endocarditis is found in older men with

repair. Surgical risk is decreased if the patient does not

genitourinary disease or after instrumentation or surgery.

have CAD, so perform a CAD screening with a nuclear

5-29

5-30

VALVULAR HEART DISEASE

aureus

(coagulase-positive),

epi dermidis

Endocarditis occurring within 2 months of prosthetic

(coagulase-negative), and gram-negative endocarditis

valve placement means the valve was seeded when the

are seen in IV drug abusers and patients with prosthetic

valve was implanted. It is harder to treat (especially if

heart valves. Other risk factors for these types of IE

include dialysis, Type 1 diabetes, bum victims, H IV, cer

adequate antibiotics, replace the valve.

tain chronic dermatologic conditions, and patients with recent surgical incisions (including median sternotomy for valve replacement). Right-sided

endocarditis

epidermidis);

If it has been

if there is no response to I round of

2 months since the prosthetic valve

placement, antibiotic treatment is generally sufficient. The valve must also be replaced if there is evidence of

and

the

resulting

septic

valve ring infection or myocardial penetration or unsta

pulmonary emboli can show up as right ventricle (RV )

ble prosthesis. These can appear as a new heart block or

enlargement and multiple lung infiltrates on chest x-ray.

a new BBB.

Onset of heart failure is a bad sign. When there is right sided endocarditis, it is almost always due to IV drug abuse (IVDA); however, IVDA-associated left-sided endocarditis occurs even more commonly! (Left-sided endocarditis has a higher incidence, and it has many more causes.)

G R

extension of the infection to the myocardium (or peri valvular abscess), failure of medical therapy, or large vegetations with systemic emboli or recurrent emboli on adequate therapy.

Occasionally, endocarditis presents only with signs of embolic events, such as black toes or septic emboli to other organs. It can also present as an illness of smol dering,

S urgery is indicated in endocarditis for refractory heart failure, usually from acute valve regurgitation,

nonspecific

For treatment of infective endocarditis, see Infectious

V d ti e

Disease, Book I .

symptoms (weight loss, fevers,

chills, night sweats, etc.), or heart failure due to valvular

Antibiotic Prophylaxis

insufficiency.

Overview

Classic physical exam findings include new regurgitant heart murmurs, Osler nodes (tender nodules on the pads

n U -

of the digits), Janeway lesions (nontender erythematous/

hemorrhagic macular/nodular lesions on the palms or soles), splinter hemorrhages (Image 5-9), and Roth spots.

Blood cultures are positive in right- and left-sided endocarditis

with

equal

frequency

(95%).

This

because there is a constant level of bacteremia in endo carditis; whereas with most other bacterial causes of

9 9

fever, the bacteremia precedes the temperature spike.

Diagnosis of endocarditis is by the Duke criteria; echo,

r i h

including TEE, is frequently used to help make the diagnosis. Diagnosis is covered in Infectious Disease, Book 1.

Know the following from the ACC/AH A 2008 Focused Update on Infective Endocarditis. S ignificant

changes

the

bacterial

endocarditis

prophylaxis prevention guidelines were made because it has become clear that infective endocarditis is more likely to occur from bacteremia caused by brushing teeth than

from medical procedures. It appears that medical proce

dures cause little if any infective endocarditis. Indications for Prophylaxis

Prophylaxis is no longer indicated for GI/GU surgeries.

Prophylaxis prior to dental procedures is now indi

cated only for patients with specific highest-risk-for-TE cardiac conditions: •

Prosthetic valves

•

Previous episode of endocarditis

•

Congenital heart disease (CHD)

•

Unrepaired cyanotic CHD

Repaired CHD within 6 months of procedure

Repaired CHD with residual defects

Cardiac transplant patients with valve lesions

Prophylaxis is no longer indicated for bicuspid aortic valve, any ASD or V SD (unless unrepaired and cya notic, or repaired with residual defect), native valvular stenosis or regurgitation, mitral valve prolapse (with or

without

murmur),

coronary

artery bypass graft

(CABG), or H CM (unless repair occurs within 6 months of procedure).

Image 5-9: Splinter hemorrhage onfingernail in endocarditis

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VALVULAR HEART DISEASE

Rheumatic fever occurs more frequently in overcrowded areas. It is the most common cause of mitral stenosis and tricuspid stenosis (Table 5-9 on page 5-32). Symptoms of valvular dysfunction generally occur, on average, 20 •

years following acute rheumatic fever infection.

Which type of ASD requires antibiotic prophylaxis before a dental procedure? Which of these require antibiotic prophylaxis: previous

SPECIFIC VALVE LESIONS

CABG? VSD? Mitral valve prolapse without

Note

murmur? Mitral valve prolapse with murmur? Prosthetic valve? Are your answers based on

Refer to Table 5-10 and Table 5-11 on page 5-34 and

the ACC/AHA 2008 guideline update? •

page 5-35 as you study these valve lesions.

Following acute rheumatic fever, how many years on average does it take for valvular

Aortic Stenosis

dysfunction to occur? •

G R

Aortic stenosis (AS) is generally due to age-related,

What common clinical symptoms do patients

calcific valve degeneration. Congenital bicuspid aortic

with aortic valve stenosis present with?

valves

usually

start

getting

calcified

and

stenotic

between ages 40 and 70 years, while the normal trileaf

Antibiotic Selection for Prophylaxis

let aortic valves become stenotic at

[Know the following:]

bicuspid aortic valve is the most common congenital

Dental procedures: All dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa require prophylaxis in high-risk patients. See Table 5-8. GU/GI procedures: Prophylaxis is not indicated in these

high-risk patients for any GI or GU procedures.

Respiratory tract procedures, or skin or musculoskeletal tissue infection: The high-risk patient should receive pro phylaxis that covers staphylococci and beta-hemolytic

streptococci.

RUBELLA

9 ri 9

Rubella during pregnancy is a common cause of patent ductus arteriosus (PDA), supravalvular aortic stenosis,

V d ti e n U

h ta

RHEUMATIC FEVER

Rheumatic fever is common

outside of the U.S., with

more than 470,000 cases worldwide. In the U.S., the latest

incidence

2-14

about

cases/100,000.

patients

valve disorder (1-2%). Less frequently, rheumatic heart mitral valve disease.

Presenting signs and symptoms include the classic triad of heart failure, angina, and syncope with exercise. Bedside physical exam with significant AS: The carotid pulse has a decreased amplitude and slowed upstroke (parvus et tardus), and the heart has a sustained apical impulse. Associated heart sounds include: •

with

(RUSB) or suprasternal notch, which radiates to

the neck

•

guished

from

Antibiotic

Situation

1 gm IM/IV

Azithn:>tllycin or clarithromycf� '

-�

Clindamycin or

unable to take oral meds

Cefazolin* or ceftriaxone

- ,�!?'

hypersensitivity reaqtion. ·

�

q, if the PCN allergy is ap ' immediate-type

*Note: Cephalosporins should not be use

referable to the heart!

Both allergic to penicillin and ,,..,.

typically has no symptoms

.•.

"'•" '

•

' j�

Note: Antibiotics (PO or parenteral) are'gi'ven 30 to 60 minut�s before the procedure, '

MedStudy

2 gmiM/IV

Cephalexin* or

negative rheumatoid factor.

Ampicillin or Cefazolin* or ceftriaxone �'1�5Cl�da,mycin or

Allergic to penicillinc!l!

cal joint deformities and a carditis

Regimen

Amoxtoillin ">,iili;Jiil

rheumatoid

associated

A paradoxical S2 split with severe AS

Table 5-8: Endocarditis Prophylaxis- Dental Procedures

arthritis by the lack of typi

The

decreased mobility of the aortic valve leaflets

mitral regurgitation (the Gallavardin effect).

· .

in rheumatic fever is distin-

Often a decreased or absent 2"d heart sound due to

where it can be confused with the systolic murmur of

Unable to take oral medications

strep screen. Joint affliction

An S4 gallop

Occasionally, an AS murmur is transmitted to the apex,

< �-,0ra1 prophY1 axts

pharyngitis,

A mid-to-late peaking, diamond-shaped systolic ejection murmur at the right upper sternal border

•

In ,

always swab throats for a

75 years old. A

disease also can cause AS, generally in the setting of

branch pulmonary artery stenosis ("peripheral PS"), and other congenital cardiac defects.

t.;

·,

�

.·

� �

""""""""' "--'

5-31

5-32

VALVULAR HEART DISEASE

Results with surgical treatment are much better, so refer

Table 5-9: Mod1fied Jones Criteria

for valve replacement early for all symptomatic patients.

for the D1agnosis of Rheumatic Fever

It is also indicated for patients with severe asymptomatic

Minor

Major

AS who develop left ventricle need CABG.

(LV) dysfunction or who

Carditis

Previous rheumatic fever

Polyarthritis

Arthralgias

Chorea

Fever

Erythema marginatum

Acute phase reactants (high sed rate or WBC)

Caution must be used with vasodilators in the treatment

Subcutaneous nodules

ECG changes: prolonged PR interval

worst prognosis of all valvular lesions, and medical

Percutaneous methods of valve replacement (known as "transcatheter" valve placement) are currently available for symptomatic patients who are high-risk surgical candidates.

To make the diagnosis: requires 2 major criteria or 1 major and 2 minor criteria and evidence of a preceding group A strep infection (positive strep test or rising or elevated[> 250 Todd units] ASO titers). The systolic ejection murmur of AS is louder with squatting, whereas the murmur of hypertrophic cardio myopathy (HCM) decreases.

of ventricular failure due to AS. Aortic stenosis has the therapy alone is not effective.

G R

Chronic Aortic Regurgitation

Chronic aortic regurgitation (AR) occurs as a result of valve deformity (e.g., bicuspid valve, rheumatic

V d ti e

fever, endocarditis, or degenerative valve disease) or an abnormal aortic root (e.g., dilation seen in Marfan syndrome, senile aortic disease, giant cell arteritis, relapsing polychondritis, or syphilis).

An ejection click sounds like a guitar string being plucked immediately after S1• This ejection click is clas sic and common in bicuspid aortic valve patients but is not heard with age-related calcific AS. Ejection clicks

Chronic

With aortic stenosis, a systolic thrill can sometimes

be felt over the upper precordium and the suprasternal

function.

Bedside physical exam with chronic AR: Chronic aortic regurgitation has several classic physical findings: •

valve. This murmur is loudest at the left sternal

border

Doppler echo is very accurate in detecting severe AS.

9 9

A decrescendo diastolic high-pitched blowing murmur caused by the regurgitation through the

notch. This thrill is a palpable sensation similar to feeling the purring of a cat.

LV volume overload, which LV dilation and a drop in LV systolic

causes

eventually causes

n U -

can also be heard in patients with pulmonic stenosis.

(3rd space) if due to the aortic leaflet, and at

the right sternal border (RSB) if due to aortic root

A left heart cath is typically used in the determination

disease (because the root is closer to the RSB). The

of AS if there is a discrepancy between clinical and

high-pitched blowing sound of this murmur indi

echo findings--or to detect concomitant coronary artery

cates a high flow, whereas mitral stenosis, which

r i h

disease.

also causes a diastolic murmur, causes a low-flow

diastolic "rumble."

Patients with AS have a high rate of coronary artery disease (CAD): 2/3 in those>

60.

113 in those 40-60 years of age and

AS severity by valve area: •

• •

•

mitral stenosis. It is thought to be due to the high leaflet and impeding mitral valve inflow by causing early closure. This murmur is not associated with a presystolic accentuation as seen in MS. •

•

on clinical presentation, given by the mnemonic SASH:

5 years 3 years Heart failure = 2 years

There are many other exam findings associated with chronic AR that have eponyms and are all related to

Survival in AS:

2° to

BP that causes "water-hammer" arterial pulses.

25 mmHg Moderate= 25-40 mmHg Severe > 40 mmHg

Mild=

A wide and bounding "Corrigan" pulse

elevated systolic and low diastolic components of

Without surgical intervention, median survival depends

•

which does sound similar to the low-flow rumble of

1.9-1.5 cm2 Moderate= 1.5-1 cm2 Severe= :S 1 cm2 Mild=

Occasionally, you hear an Austin Flint murmur,

pressure regurgitant jet striking the anterior mitral

Mean gradients are also frequently used: •

•

pulsations; e.g., Becker sign= visible pulsations of the retinal arteries; de Musset sign = bobbing of the head with the pulse; Muller sign

bobbing of uvula

during systole.

Angina=

Chest x-ray shows an enlarged left ventricle and

Syncope=

may show dilation of the ascending aorta. Aortic

angiography can be performed at the time of cardiac

VALVULAR HEART DISEASE

•

When should valve replacement occur for aortic valve stenosis?

•

Name 2 conditions that cause chronic aortic regurgitation.

•

What is the usual treatment for acute aortic regurgitation?

•

When the mitral stenosis is more severe, is the STOS interval smaller or larger?

•

Which type of murmur occurs in mitral stenosis?

•

Which mitral lesion is associated with

G R

hemoptysis?

cath and is the gold standard to diagnose AR-although it is more frequently diagnosed with echo. Patients

with

chronic

should

monitored

with echocardiograms to follow chamber size and LV function. Treat chronic and severe AR with vasodilators. Routine use of vasodilator therapy is no longer recommended for non-severe AR. ACE Is/ARBs are typically used, along with diuretics to treat symptoms. Valve surgery is indicated if the patient is symptomatic or when echocardiogram

shows

end-systolic

dimension

55 mm, LV end-diastolic dimension > 75 mm, or E F <55% (remember AR: the 55155 rule!). >

Intraaortic balloon pump placement is contraindicated

9 ri 9

in patients with aortic regurgitation.

Acute Aortic Regurgitation

Native acute AR is normally caused by a flail leaflet due to:

h ta

•

Endocarditis

•

Type A aortic dissection

Trauma

Prosthetic valve acute AR can be caused by: Tissue valve leaflet rupture

Mechanical valve closure problem (e.g., thrombosis)

Paravalvular regurgitation due to infection

edema and low cardiac output. Because the cardiac output and BP are low, there is no bounding arterial pulse. The diastolic murmur is short because it ends when the ventricular pressure rises to the level of the low aortic pressure. The LV in these patients does not have time to compensate for the LV volume overload. Patients with significant acute AR and heart failure a

reversible

cause

almost

Mitral stenosis (MS) is relatively rare in the U.S. It is

almost always due to rheumatic fever. Other causes are SLE, rheumatoid arthritis, and severe valve calcification. Atrial fibrillation is common. MS can cause heart failure

(HF), but sometimes 2° pulmonary hypertension is the main physical finding.

Bedside physical exam with MS:

Patients have a

diastolic murmur with a diastolic opening snap (OS) caused by the tensing of the chordae tendineae and ste

notic leaflets. The time interval between the second heart sound (S2) and the OS or the S2-0S interval is inversely related to the severity of the MS: the more severe the

MS, the higher the left atrial (LA) pressure, and thus the earlier the mitral valve is forced open in diastole, the smaller the S2-0S interval. As mentioned in heart sounds, the S 1 is accentuated and can also have a snapping quality. The diastolic murmur is often described as a "rumble," which suggests low flow, in contrast to the high-pitched, high-flow diastolic

always

The chest x-ray shows the following triad: 1) Prominent pulmonary artery revascularization

Patients with acute AR present with severe pulmonary

without

Mitral Stenosis

murmur heard in aortic regurgitation.

immediate surgery.

V d ti e n U

Image 5-10.· Mitral stenosis with enlarged left atrium

need

An enlarged left atrium (see straightening of left atrial border in Image

5-10 on page 5-33)

3) Normal-sized LV The ECG also shows the enlarged left atrium. Do an echo to confirm the diagnosis. Hemoptysis can occur in patients with MS; it is due to rupture of the pulmonary bronchial

vessels

hypertension.

distended

pulmonary

venous

5-33

5-34

VALVULAR HEART DISEASE

Table 5-10: Valve Defect

Heart Defects and Associated Sounds (1 of

Murmurs

Aortic stenosis

Clicks

Change in Heart

Pulse Waveforms;

Sounds

a/vWaves

S: Ejection

Absent 82 (occ); S4;

Slowed carotid

click if congeni

Paradoxically split S2

upstroke

D: Short diastolic murmur

s3 if severe

Thready

Chronic aortic

S: Occasional early systole SEM.

s3 if severe

regurgitation

D: l ) High pitched, decrescendo

tal or bicuspid Acute aortic

regurgitation "Corrigan pulse"; "Water-ha.mmer pulse"

early to holodiastolic (regUrgitation through the valve) 2) AustinFlint: low, rumbling diastolic (regurgitant stream striking the anterior mitral .leaflets) Mitral stenosis

D: Diastolic rumble

D: Opening

S 1 is enhanced, some

Large left

snap (only

times "snapping." May

y descent

diastolic click!)

be silent if severely

waves and

calcified MVP with

S: MVP: Mid-

murmur; chronic

CMR: Pansystolic constant

mitral regurgita-

mul;ll1ur

s3 if severe; s4

tion (CMR) Acute mitral

S: Pansystolic decrescendo at apex

Large left

s3 if severe

regurgitation

vwaves

D: Diastolic at LSB

Tricuspid

Giant right

stenosis

Tricuspid

D: Systolic at LLSB

waves

Large right

regurgitation

v '�

waves

Pulmonic

Persistently/wl4ely split

Large right (jugular)

stenosis

wave

S: Holosystolic at LLSB

VSD ASD-ostium

S: SEM at LSB (increased flow

secundum

aq()s,s pulmonic valve)

ASD-ostium

S: SEM at LSB (increased flow

primum

across pulmonic valve); also often

Fixed-split S2

associated TR or MR murmur Coarctation of the aorta

HCM

Brisk carotid upstroke

S: Harsh midsystolic murmur

that is BIFID in 2/3 PDA

So.,t, Q: Continuous "machinery" ..

murmur at LUSB Note that S4 is also heard in ischemic heart disease, diabetic cardiomyopathy, and hypertensive heart disease with concentric hypertrophy. Note: Right-sided murmurs sound louder on Inspiration; lEft on Expiration; all right-sided valve problems can rarely be caused by carcinoid. Cannon

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

VALVULAR HEART DISEASE

Table

LVE

(2 of 2) Valve Defect

Other:

CXR

Murmur Louder with: Squatting*, expiration

5-11: Heart Defects and Associated Sounds

Sustained apical impulse; etio: bicuspid valve

Aortic stenosis

Âˇ

classic triad is LVF, angina, and

after PVCs

syncope with exercise Squatting*, expiration

LAE

Mitral stenosis

Etio: virtually always rheumatic fever SSx: hemoptysis. Secondary pulmonary HTN

Squatting*, expiration

LVE

Etio: congenital, endocarditis, or dilated regurgitation

aortic root from: Marfan, VSD, arteritis, polychondritis, syphilis

Squatting*, expiration

Standing or Valsalva:

Normal

LAE

Cardiogenic shock and pul edema

Acute aortic

Consider aortic dissection

regurgitation

Etio of MVP: congenital; ischemia

MVP with murmur;

longer-moves earlier

chronic mitral

into systole; sustained

regurgitation (CMR)

handgrip, expiration Squatting*, expiration

Normal

Etio: endocarditis, Ml with papillary muscle

Acute mitral

ischemia or rupture, chordae tendineae rupture;

regurgitation

SSx: pul edema Inspiration

RVH; enlarged

Etio: virtually always congenital-rarely caused by

pulmonary artery

rheumatic fever and carcinoid; congenital

Pulmonic stenosis

type

usually does not progress Squatting*, inspiration

RAE

TS is rare; Etio: usually rheumatic fever but also

Tricuspid stenosis

congenital and carcinoid synd. with carcinoid, pt. usually also has TR SSx: venous congestion Squatting*, inspiration

RVE

Etio: usually dilation from pul HTN;

Tricuspid regurgitation

other: rheumatic fever, endocarditis (IVDA), carcinoid. L iver pulsations, ND Handgrip

RVE+LVE

Consider in new MI with new systolic murmur

VSD

RVE;

ECG: RAD, RBBB

ASD -ostium secundum

shunt vascularity RVE

ECG: LAD , RBBB

ASD---ostium primum

Coarctation of the aorta

Rib notching, loss of aortic notch Standing, Valsalva.

LVE

Note: Sustained handgrip

Apical impulse may have double- or

HCM

triple-taps

decreases murmur. Calcification of

PDA

ductus arteriosis *Squatting or lying down; or raising legs if already supine. ... Persistently/widely split S2 (still varies with inspiration but never goes away) occurs with pulmonic stenosis, PE, RBBB , LV ectopic beats. ... Fixed split S2 (A2-P2 interval remains the same throughout breathing cycle) from ASD . ... Paradoxically split S2 (P2 before A2) is caused by severe HCM, LBBB , RV ectopic beats, AS, and PDA.

ÂŠ

2014 MedStudy

5-35

5-36

VALVULAR HEART DISEASE

Pregnancy: The increased blood volume in pregnancy

MVP. Most MVPs are considered a normal variant; in

can cause a precipitous exacerbation of MS. The initial

these, the chordae tendineae are weakened, causing a

presentation of MS in a pregnant patient may be new

billowing of the otherwise normal mitral valve leaflets.

onset atrial fibrillation and pulmonary edema. Heart

On the other hand, myxomatous changes in the mitral

rate and volume control (beta-blockers and diuretics)

valve leaflets (determined by echo) invariably progress

are an essential part of treatment. If anticoagulation is

to mitral regurgitation. Many symptoms (dyspnea, panic

necessary, never give warfarin in the I 51 trimester; it is

attacks, chest pain, etc.), previously attributed to MVP,

teratogenic. Give adjusted-dose heparin instead.

have been shown to occur with no greater frequency

All

nonpregnant

patients

with

MS-caused

atrial

fibrillation should be anticoagulated with warfarin. Do

percutaneous

valvotomy

patients

Bedside physical exam with MVP: with

symptomatic MS or asymptomatic MS with pulmo nary hypertension (pulmonary artery systolic pressure >

than in otherwise healthy people.

50 mmHg at rest or > 60 mmHg with exercise).

These

patients

have a midsystolic click (followed by a mid-to-late systolic murmur [click-murmur syndrome] if there is associated MR). The murmur of MVP is like the murmur in hypertrophic

Surgical mitral valve replacement is less desirable but

cardiomyopathy

frequently is a necessary alternative if valvular anatomy

increases the intensity of the murmur. The click and

(HCM)

that

decreased

preload

is not favorable for percutaneous valvotomy (especially

murmur become louder and move earlier into systole

if there is severe calcification of the valve) or significant

with standing or Valsalva, both of which decrease pre

(more than mild) mitral regurgitation is present.

load and, hence, LV volume. (An earlier click means a longer murmur.) This gives the clue for how you can tell the difference between an ejection click (aortic or

Chronic Mitral Regurgitation Chronic

mitral regurgitation (MR) can

pulmonary stenosis)

and the midsystolic

click-an

due to

ejection click is fixed, whereas the midsystolic click

rheumatic heart disease, mitral valve prolapse (below),

varies in timing with changes in the patient's position.

annulus dilation from left ventricular dilation, prior

Stand the patient up, and the midsystolic click sounds

episode of endocarditis, and/or ischemic effects on

just like an ejection click. Squatting or supine position

the papillary muscle (from coronary artery disease or

increases LV size and causes the click to occur later,

Ml). Chronic MR presents differently from acute MR.

thereby shortening the murmur. Dynamic auscultation is

Because the heart has an enlarged left atrium in the

required to diagnose MVP clinically.

chronic form, there is less back pressure to the flow across the incompetent mitral valve, resulting in a constant intensity, holosystolic murmur instead of decre

Acute Mitral Regurgitation

scendo (as in acute MR). Atrial fibrillation frequently

Acute mitral regurgitation

develops. In both severe chronic and acute MR, the S1

with acute-onset pulmonary edema.

is soft or absent and S2 is widely split. (The aortic valves close early because of decreased volume ejected from the left ventricle.) An S3 is common in severe MR. The left ventricular ejection fraction (LV EF) in MR is frequently normal or above normal, because LV outflow

(AMR) commonly presents

Causes of native valve AMR include: •

Flail leaflet (due to endocarditis, MVP, or trauma)

•

Papillary muscle ischemia or rupture (MI, trauma)

•

Chordae tendineae rupture (endocarditis, acute

2 routes of exit during systole (forward through

rheumatic fever, trauma, spontaneous)

the aorta and backward through the regurgitant mitral

Causes of prosthetic valve AMR include:

now has

valve). Significant MR should be treated with diuretics and

afterload

reducing

agents

(ACEis/ARBs).

•

surgery if the patient is symptomatic or if asymptomatic

•

with:

•

LVEF

•

LV enlargement with left ventricular end-systolic

65%, and/or

diameter> •

(if

murmur at the apex. Echocardiogram shows a hyperac tive LV with normal-to-high ejection fraction and a

40 mm, or

possible)

Mechanical valve closure problem (e.g., thrombosis) Paravalvular regurgitation due to infection

Bedside physical exam with AMR: Decrescendo systolic

normal-sized left atrium. There are large, left-sided

pulmonary hypertension.

Repair

Tissue valve leaflet rupture

preferable

replacement.

Percutaneous valve repair is now available.

waves on wedge pressure tracing. Treat with afterload reduction and diurese. Unlike severe AR, intraaortic balloon pump can be helpful for patients in

heart failure from AMR. Urgent surgery is often required.

Mitral Valve Prolapse Mitral valve prolapse (MVP) is the most common valvular problem seen in practice (up to

2.4%) and is

more common in women. There are different causes of

VALVULAR HEART DISEASE

Bedside

physical exam

with TR:

Patients have a

holosystolic murmur along the lower left sternal border (increases with inspiration) that does not radiate to the axilla. Severe TR can cause a parasternal heave, liver •

What should you consider in a pregnant

pulsations, venous distention, ascites, and lower extrem

woman with new onset of atrial fibrillation and

ity edema (signs of RV failure). There are large, jugular

pulmonary edema? •

Describe the murmur sometimes heard with

Diagnose with echo. Treat the underlying disease.

MVP. Does that murmur's intensity decrease

•

or increase with standing? With Valsalva

Antibiotic treatment is usually sufficient for endocarditis;

maneuver?

the valve rarely needs to be removed, unless the cause is

Carcinoid usually results in what type of tricuspid murmur?

•

On physical exam, in patients with tricuspid

Candida. Surgery also can be indicated in circumstances of severe destruction of the valve.

regurgitation, what large waves are noted on the

Pulmonic Stenosis

jugular waveform?

Pulmonic stenosis is virtually always congenital, and it

True or false? Pulmonic stenosis is virtually

typically does not progress! It is a fairly common con genital valve anomaly in adults. Rarely is it caused by

always acquired. •

waves, reflecting the backflow through the tricuspid

valve during ventricular contraction.

Ebstein anomaly is occasionally associated with which structural and electrical abnormalities?

rheumatic heart disease or carcinoid. It may cause RV hypertrophy. Although it generally is not seen along with other abnormalities, it does occur in Noonan syndrome, in which the patient has low-set ears and hairline.

Tricuspid Stenosis

Bedside physical exam with severe pulmonic stenosis:

Tricuspid stenosis (TS) is rare. Causes are rheumatic

Patients have an ejection click and a prominent jug

fever (usual), congenital, carcinoid syndrome, and endo

ular a wave, which is caused by backflow during

carditis. If the cause is carcinoid, the TS is generally

atrial

found in association with tricuspid regurgitation (TR).

right ventricle.

Note: Carcinoid can affect either right-sided heart valve and typically implies a hepatic tumor if valvular involve ment is present. (The pulmonary vascular bed is generally

contraction

against

inadequately

emptied

If needed, open the stenotic pulmonic valve with balloon valvuloplasty.

quite effective in removing the active 5-HIAA products that lead to valve damage.) Patients have systemic venous congestion without pulmonary venous congestion or pulmonary hypertension.

Pulmonic Regurgitation Pulmonic

regurgitation

typically

secondary

pulmonary hypertension (e.g., primary, cor pulmonale,

Bedside physical exam with TS: Patients have a diastolic

mitral stenosis), but it may be due to a primary valve

murmur along the left sternal border, which increases

lesion (congenital, rheumatic heart disease, endocarditis,

with inspiration (as do all right-sided murmurs). They

carcinoid). Pulmonary artery pressure is

have a giant a wave, caused by backflow during atrial

patients with secondary pulmonic regurgitation.

60 mmHg in

contraction against a stenotic tricuspid valve. There may be ascites and lower-extremity edema.

Ebstein Anomaly

The ECG shows the tall, peaked P waves in II and VI (evidence of the right atrial hypertrophy) but no indications of right ventricular hypertrophy (RVH). Chest x-ray shows an enlarged right atrium.

With Ebstein anomaly, the tricuspid septal leaflet is positioned lower in the ventricle than normal (apically displaced)-so the RA appears huge and the RV small. Tricuspid regurgitation (TR) murmur is common. It is

Treat the underlying disease and perform surgery.

occasionally seen with atrial septal defect (ASD) and with WPW syndrome.

Tricuspid Regurgitation Tricuspid regurgitation (TR) often is a functional result

VALVE SURGERY

of RV dilation, which can be caused by end-stage left

In general, valve surgery is indicated for any valve

ventricular failure,

pulmonary

embolism,

other

causes of pulmonary hypertension. TR can also be caused

rheumatic

heart

disease,

endocarditis,

carcinoid, and congenital disease-Ebstein anomaly. Endocarditis affecting the tricuspid valve is typically seen in drug abusers, and it is often caused by staph; also consider Candida.

problem if the patient is symptomatic at rest or with low levels of exertion. Even though there is high mortality, valve surgery is better than no surgery in patients with severe valve disease and ventricular failure (since the natural history in these cases is 100% early mortality).

5-37

5-38

ARRHYTHMIAS

3rd intercostal space, with patient leaning forward

Bioprosthetic valves are less durable (especially in young patients and those on hemodialysis) but do not

and exhaling; also, low-pitched late-diastolic rumble

require anticoagulation. These are indicated in patients

(A ustin Flint)

with a life expectancy of

5-10 years and those with

contraindications to anticoagulation (chronic bleeding problems, ulcers). They also are often given to women of childbearing age to avoid having to use anticoagulants during pregnancy. Mechanical valves are used for all others and do require anticoagulation, but they are very durable-typically

•

Mitral stenosis: hemoptysis, opening snap, lowpitched diastolic murmur at the apex

Valsalva (one last time): decreases the murmur of aortic stenosis (A S), increases the murmur of hypertrophic cardiomyopathy, and increases the murmur of mitral valve prolapse.

lifelong in most cases.

ARRHYTHMIAS

Balloon valvuloplasty is the procedure of choice in pulmonic valve stenosis and frequently mitral stenosis but not aortic stenosis due to a very high short-term restenosis rate

(6-12 months).

MECHANISMS OF ARRHYTHMIAS The 3 usual mechanisms of abnormal rhythms are

For mitral regurgitation (MR), if surgery is required,

reentry, triggered activity, and automaticity. The reentry

do valve reconstruction whenever possible because

is the most common mechanism of arrhythmias, espe

it has better outcomes and about half the morbidity of

cially AV node reentrant tachycardia (AVNRT), atrial

MV replacement. Reconstruction is valve repair and/

flutter, and most ventricular tachycardias. AVNRT is the

or annuloplasty with an annuloplasty ring, and is espe

most common type of reentrant tachycardia-hence it

cially likely to be done with MVP, ruptured chordae,

also is the most common supraventricular tachycardia

flail leaflets, endocarditis, and annular dilation. Valve

(SV T). Be able to diagnose all rhythms at a glance (see

replacement is usually necessary in MR that is due to

ECGs on page

5-60).

rheumatic fever. Newer "edge-to-edge" percutaneous MV repair, where a device (a clip) is placed across the two leaflets in their mid-part, creating a double-orifice mitral valve, is now being performed; this procedure is ordinarily reserved for patients who are high risk for traditional repair. Similarly, percutaneous aortic valve replacement is now available for patients who are at high risk for surgery. The major determinants in prognosis after valve surgery

SICK SINUS SYNDROME Sick sinus syndrome causes any one (or combination) of sinoatrial node problems, including sinus bradycardia, sinus pauses/sinus arrest, and tachy-brady syndrome (typically baseline sinus bradycardia or sinus pauses with intermittent episodes of rapidly conducting atrial fibrillation/atrial flutter). These patients generally do not need electrophysiologic testing. Because prognosis is

include ejection fraction, degree of symptoms, and type

good, there are only

of valve surgery (valve repair is better than replace

pacemaker:

ment).

Echocardiography is best

for checking for

prosthetic valvular function. A transesophageal echocar diogram (TEE) is especially useful for checking mitral

2 indications for treatment with a

1) Symptomatic patient 2) Patient with tachy-brady syndrome where treatment of tachyarrhythmias might precipitate or worsen

valve prosthesis. Fluoroscopy is also a useful tool for

bradycardia

documenting leaflet motion with mechanical valves if valve dysfunction is suspected. When anticoagulating mechanical valves, keep the INR

HEART BLOCK

2.0-3.0 for the aortic valve and 2.5-3.5 for the mitral

151 degree heart block: PR interval

valve. A mechanical mitral valve has a higher risk for

be caused by medications and generally requires no

a thrombus formation compared to an aortic (hence the

treatment.

higher INR requirement). Therefore, if holding warfarin for a procedure or surgery, then bridging anticoagula tion with unfractionated heparin is recommended for mechanical mitral valves.

heart block

(Mobitz

Wenckebach):

gradual prolongation of PR interval until QRS drops; return PR interval shorter than last conducted PR interval. I t can occur during periods of high vagal tone athletes. It generally does not require treatment unless it is causing symptoms.

[Know:] A ortic stenosis: suprasternal notch thrill with systolic murmur, paradoxically split s2 •

degree

200 ms. Can

during sleep (obstructive sleep apnea) or in endurance

Final Pearls about Murmurs

•

2"d

Chronic aortic regurgitation: early diastolic, blowing, decrescendo murmur heard best at left sternal border,

2nd degree heart block (Mobitz 2): abrupt loss of P wave conduction to the ventricle with no evidence of grad ual prolongation. Generally, it indicates higher grade AV block, and associated symptoms can necessitate pacemaker placement.

ARRHYTHMIAS

The normal AV block is 2:1 with a ventricular rate of half the atrial rate. If it is 2: 3: 1, the cause is either medications or can suggest advanced AV conduction system disease. Systemic embolization (most notably •

What are the major prognostic factors after

•

Describe the abnormal heart sounds found in

AS, chronic AR, and MS. What is the treatment sequence for atrial flutter?

•

What procedure can cure the most common types of atrial flutter with

in both disorders. Vagal maneuvers or adenosine cannot terminate atrial

•

3rd

TINstroke) can occur due to atrial flutter or atrial fibrillation; thus, anticoagulation needs to be considered

valve surgery?

85-95% success rate?

degree heart block (complete heart block): None of

the P waves are conducted to the ventricles, and there is often a regular junction (40-60 bpm) or ventricular (20-40 bpm) escape rhythm. Permanent pacing is indicated if there is a Mobitz 2 or complete heart block-especially if symptomatic. See Arrhythmias and Blocks, starting on page 5-22, for more detailed pacing criteria post-MI. To differentiate between AV node block vs. infranodal block: AV node block typically has narrow QRS com plexes, has escape focus rate

> 40 bpm (typically

40-60 bpm), and is responsive to atropine. Infranodal block (involving the His-Purkinje system) is mostly associated with widening of the QRS complex.

flutter; however, they can slow the ventricular rate and allow better diagnosis. Rule out pulmonary emboli (often multiple) and thyroid disease-especially if there is no heart or lung history. The

most

effective

treatment

for

atrial

flutter

synchronized DC (direct current) cardioversion. Always shock if the patient is hemodynamically compromised. Do not continue DC

cardioversion if

the patient

repeatedly reverts back to atrial flutter. Antiarrhythmic drugs can be used for nonemergent cardioversion. I V ibutilide is most effective and can be considered a I st line pharmacologic cardioversion for atrial flutter; however, be aware that it can cause QT prolongation (8%) and torsades de pointes. Make sure potassium and magnesium levels are normal prior to administering ibutilide to minimize risks of torsades. Procainamide, flecainide, and propafenone can be used as well. See Antiarrhythmic Therapy on page 5-45. In patients with atrial flutter and preexcitation syndrome

SUPRAVENTRICULAR TACHYCARDIAS Atrial Flutter Typical

(Type

the

common

form, has a characteristic atrial rate of

300 bpm

atrial

flutter,

(240-340)---commonly with a 2:1 AV block. Pay close attention for atrial flutter when any ECG is shown with a heart rate of 150 bpm; atrial flutter waves at 300 bpm with 2:1 AV block gives a heart rate of 150 bpm. Atrial flutter can be: •

typical counterclockwise rotation around the right

(WPW), avoid digoxin, calcium channel blockers, and beta-blockers. See WPW, page 5-42. Radiofrequency ablation is a treatment modality that can cure the most common types of atrial flutter (success rate 85-95%), and it is used for persistent or recurrent atrial flutter, although recent studies have suggested it is a reasonable I st line approach in some circumstances. Anticoagulate patients with atrial flutter, as you would for atrial fibrillation (see next). Indeed, up to 60% of patients with atrial flutter have had atrial fibrillation in the preceding year.

atrium, characterized by negative sawtooth flutter waves in II, III, and a VF (with positive deflection in V1);or •

clockwise, characterized by positive flutter waves in

Atrial Fibrillation Overview

ECG leads II, III, and a VF (with prominent negative

Atrial fibrillation (A-fib) is the most common sustained

deflection in V 1).

arrhythmia. Ventricular rhythm is irregularly irregular

These 2 atrial flutter types share the same right atrial reentrant circuit around the cava-tricuspid isthmus (circuit running between the inferior vena cava and the tricuspid valve).

with ventricular rate generally in the range of 120-180 bpm in the absence of drug therapy. Many patients with atrial fibrillation have structural heart disease, and it is commonly associated with hypertension, heart failure, valvular heart disease, coronary artery disease, chronic

Atrial flutter is generally an indication of disease,

lung disease, and obstructive sleep apnea.

most often either organic heart disease or pulmonary

A-fib can be classified as first detected (only I diagnosed

disease. Flutter is a relatively unstable rhythm and often spontaneously converts to either atrial fibrillation or a normal sinus rhythm.

episode), paroxysmal

(2: 2 episodes, self-terminating, each 24 hours), persistent (2: 2 episodes, each lasts > 7 days), and permanent (> 6-12 months). lasts :S 7 days, most

The symptoms of A-fib vary widely between patients.

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5-39

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ARRHYTHMIAS

Some patients are asymptomatic and others have severe,

A-Fib Rhythm Control: Pharmacologic

functionally disabling symptoms. Complications are

Cardioversion

embolic events-mainly stroke, and tachycardia-induced cardiomyopathy.

When attempting pham1acologic cardioversion, use these guidelines-again, use is based on duration of

With new-onset A-fib or in A-fib not responsive to the usual treatment, consider hyperthyroidism, untreated or undertreated obstructive sleep apnea, hypomagnesemia,

symptoms. •

alcoholism/cocaine abuse, excessive caffeine (energy beverages), and nicotine as possible causes.

•

1st line: dofetilide, ftecainide, ibutilide, or propafenone (previously, dronedarone*)

Rhythm Control vs. Rate Control

2nd line: amiodarone (Exception: If< 48 hours and poor cardiac function, amiodarone is 1st line.)

2 choices for the treatment of A-fib:

1) Rhythm control (restoration and maintenance of sinus rhythm)

*Do not prescribe dronedarone to patients with class I V heart failure or those who have had decompensated heart failure in the past month, especially if LVEF

2) Rate control (control of ventricular response)

There are no significant differences in mortality or morbidity between the

I st line: dofetilide

2nd line: amiodarone or ibutilide

For A-fib< 7 days: o

Treatment of Atrial Fibrillation

You have

For A-fib> 7 days:

2 treatments. Rate control is the

common strategy for asymptomatic or minimally symp

35%, because it causes increased mortality in these

patients.

addition,

dronedarone

should

not

used in patients who have had pulmonary toxicity on amiodarone or elevated LFTs.

tomatic patients, while rhythm control is often selected for significantly symptomatic and younger patients. For patients with hemodynamic instability, ongoing

Maintenance Drugs for Rhythm Control

myocardial ischemia, symptomatic hypotension, angina

Pharmacological therapy can be useful in patients with

or heart failure, emergent/urgent direct-current (DC)

recurrent paroxysmal or permanent A-fib to maintain

cardioversion is recommended.

sinus rhythm. Before initiating antiarrhythmic drug therapy, treatment of precipitating or reversible causes of A-fib is recommended. Deciding which drug to use is

A-Fib Rhythm Control: DC Cardioversion

based on the presence of structural heart disease (safety)

DC cardioversion is the most effective method to

and, to a lesser degree, on efficacy. Catheter ablation is

restore sinus rhythm. Pharmacologic rates of successful

useful in maintaining sinus rhythm for selected patients

cardioversion are lower and depend on the antiarrhyth

with significantly symptomatic, paroxysmal A-fib who

mic drug used and clinical scenario. If possible, DC

have failed treatment with an antiarrhythmic drug and

cardioversion should be carried out under sedation, with

have a normal or mildly dilated left atrium, normal or

appropriate cardiac and hemodynamic monitoring.

mildly reduced LV systolic function, and no severe

Emergent/Urgent DC cardioversion is recommended for patients with hemodynamic instability (angina pectoris, MI, shock, or pulmonary edema), ongoing myocardial ischemia, symptomatic hypotension, angina or heart failure, and WPW syndrome with rapid ventricular rate.

pulmonary disease. Catheter ablation is less useful (however, can be considered) in treatment of patients with symptomatic persistent A-fib. Selection of antiarrhythmic drugs: •

Important points regarding DC cardioversion: •

none, sotalol, and dronedarone; if ineffective, then amiodarone, dofetilide, or catheter ablation.

With slow A-fib, consider inserting a temporary pacemaker before DC cardioversion because the

•

35%): amiodarone or dofetilide

catheter ablation.

have asystole after cardioversion. •

TEE-guided cardioversion is done frequently,

Coronary artery disease: dofetilide or sotalol; if ineffective, then amiodarone or catheter ablation.

especially if the time of onset of the A-fib is unclear. It is fast and cost-effective. •

Heart failure (EF <

(definitely not dronedarone!); if ineffective, then

patient could have sinus nodal disease and may •

No or minimal heart disease: ftecainide, propafe

•

Just as with atrial flutter, do not continue DC

Hypertension: o

Left ventricular hypertrophy (LVH) present: Use amiodarone; if ineffective, then catheter ablation.

cardioversion if the patient repeatedly goes right back into A-fib shortly after being shocked.

Note: In what other scenarios do you not shock a patient with an abnormal tachycardic atrial rhythm (but

LVH not present: Use ftecainide, propafenone, or sotalol. If these fail, then go to amiodarone, dofetilide, or catheter ablation.

stable hemodynamically)? Digitalis intoxication and hypokalemia.

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ARRHYTHMIAS

blockers (verapamil, diltiazem) should be used with cau tion to slow the ventricular response in patients with hypotension or heart failure because of negative inotro pic effects. •

In what circumstance is immediate DC

I V digoxin or amiodarone is used to control the heart

cardioversion indicated for A-fib? •

rate acutely in patients with A-fib and HF who do not have an accessory pathway.

What can happen after DC cardioversion to the patient who has A-fib with a slow rate? What

lf exertional symptoms related to A-fib are present, assess

intervention prevents this complication? •

heart rate control during exercise, adjusting pharmaco logical treatment to keep the rate in physiological range.

According to the 2013 guidelines, what HR is an acceptable target for patients with A-fib and

Digoxin is useful to control the heart rate at rest in

stable ventricular function? For others, how is

patients with A-fib with HF, LV dysfunction, or for

strict control of heart rate defined? •

sedentary individuals.

For patients undergoing cardiac surgery,

Radiofrequency ablation of the AV node with subsequent

what medication should be used to prevent

permanent pacing is a treatment for patients with refrac

postoperative A-fib?

tory A-fib and for those who cannot tolerate the meds needed for rate or rhythm control. This strategy provides

Use of classIC agents for atrial fibrillation: The unopposed use of class IC agents

definitive rate control but does not cure the underly (e.g.,

concomitant AV nodal blocking agents) can organize atrial fibrillation into atrial flutter conducting to the ventricles much more rapidly. This rapid conduction could degenerate into ventricular tachycardia ( VT) or ventricular fibrillation ( VF). To avoid this potentially fatal event, always use class TC agents with AV nodal agents such as

beta-blockers,

non-dihydropyridine

calcium channel blockers, or digoxin. Reminders for rhythm control of atrial fibrillation: I) Dofetilide and sotalol require hospital monitoring to

initiate therapy.

ing

atrial

fibrillation-hence,

patients

still

require

anticoagulation. In many patients, A-fib originates as abnormal impulses arising in the pulmonary veins. Radiofrequency ablation, or isolation of the pulmonary veins, is becoming increas ingly popular in treating recurrent, drug refractory, symptomatic A-fib, although it is not yet established as Ist line therapy. Postoperative A-Fib

For patients undergoing cardiac surgery, give an oral beta-blocker to prevent postoperative A-fib (unless

2) Dronedarone cannot be used in the New York Heart

contraindicated). For those who develop postoperative

Association (NYHA) class I V heart failure (HF) or

A-fib, achieve rate control with AV nodal blocking drugs

if HF exacerbation in past 4 weeks.

(beta-blockers, calcium channel blockers, or digoxin). Routine postoperative amiodarone is not indicated for

A-Fib Rate Control

The 2013 update to the ACC/AHA Practice Guideline:

the prevention of atrial fibrillation.

Management of Patients with Atrial Fibrillation states

Anticoagulation for Atrial Fibrillation

that a resting heart rate < II 0 bpm is acceptable and is

Before and After Cardioversion

as good as strict control if stable ventricular function (LVEF

40%) and there are no or acceptable symp

toms related to the arrhythmia; though uncontrolled tachycardia may, over time, be associated with a revers ible decline in ventricular performance. Strict control of

If it has been< 48 hours since the onset of A-fib, cardia vert most patients without any preceding anticoagulation. If it has been

48 hours since the onset of A-fib (or

duration of A-fib is unknown) and the patient is stable,

heart rate is considered 80 bpm at rest or 11 0 bpm during

you must achieve adequate anticoagulation x3 weeks

a 6-minute walk.

before you attempt cardioversion. As an alternative to

Use beta-blockers (atenolol, metoprolol) or calcium channel blockers (verapamil, diltiazem) for rate con trol at rest and with exercise. Digoxin can have a synergistic effect for rate control when combined with these medications. A-fib with HF: acute setting and no preexcitation-I V beta-blockers (esmolol, metoprolol, or propranolol) to slow ventricular rate or amiodarone to slow ventricular rate and possibly restore sinus rhythm. Calcium channel

MedStudy

preceding anticoagulation, it is reasonable to perform TEE, and if there is no identifiable thrombus, perform a cardioversion. After cardioversion: Treat with low-molecular-weight or unfractionated heparin until INR

2-3 on warfarin. As

an alternative to heparin/warfarin, one of the novel oral anticoagulants (NOACs) can be considered.

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ARRHYTHMIAS

Chronic Anticoagulation

If no P wave is seen (buried in QRS) or is seen at the

Antithrombotic therapy to prevent thromboembolism is recommended for all patients with A-fib (irrespective of rate or rhythm control strategy), except for those with lone A-fib (age

60 years without heart disease and

end of the QRS (very short R-P interval), the patient has AV node reentrant tachycardia (AVNRT). Representing 60-70% of regular S VT, AVNRT is the most common reentrant tachycardia.

without risk factors) or contraindications. The selection

If a P wave is somewhere in ST-segment (short R-P

of the antithrombotic agent should be based upon the

interval) AV reentrant tachycardia ([AVRT]; 20-30%

absolute risk of stroke. Patients with rheumatic mitral

of regular S VT) should be considered.

stenosis and prior thromboembolism are at highest risk. For patients with non-valvular A-fib (without rheumatic mitral stenosis or prosthetic valves), the CHADS2 scoring system is often used for risk stratification: •

CHF during last year or EF

If a P wave is seen after a T wave (long R-P interval), atrial tachycardia (10% regular S VT) is most likely the diagnosis. In acute management of narrow QRS complex, regular tachycardia treatment options include beta-blockers, adenosine, calcium channel blockers, or

35% (any history):

carotid sinus massage.

I point

HTN (prior history): I point

Most S VTs are due to a reentrant mechanism. Again,

Age 2: 75: I point

the most common S VT is AVNRT. Rate is typically

•

OM: 1 point

150-250 bpm (although it can be slower or faster).

•

Prior Stroke, TIA, or embolic event: 2 points

•

Radiofrequency

Meds based on CHADS2: •

•

0 points

highly

successful and

I st line long-term therapy. Situations where ablation

symptoms,

I point= oral anticoagulation or ASA =

is preferred include hemodynamic instability, severe

ASA alone

2 points or more

ablation

can be considered equally with medical therapy as

failed

medical

therapy,

public

safety

(pilots and bus drivers), and clear patient preference.

oral anticoagulation

If medical therapy is chosen, beta-blockers, calcium

Oral anticoagulation can be achieved with vitamin K

channel blockers, or digoxin are

antagonists or new anticoagulant agents (dabigatran,

followed by antiarrhythmic drugs (typically flecainide

rivaroxaban, and apixaban). New agents do not require

or propafenone if there is no structural heart disease).

monitoring

(INR);

however,

they cannot

I st line options,

used

in patients with prosthetic valves, rheumatic mitral stenosis, renal insufficiency, and advanced liver disease. Dabigatran is useful as an alternative to warfarin for prevention of stroke and systemic thromboembolism in patients with A-fib and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve, significant valve disease, severe renal failure (Cr clearance I 5 mL/min) or advanced liver disease (impaired baseline clotting function).

WPW Wolff-Parkinson-White

([WPW];

syndrome): P R interval is

preexcitation

0.12 seconds due to a

delta wave and symptoms of tachycardia. Total QRS is > 0.12 seconds because of the fusion between the

impulse that

uses the normal conduction

system

and that which uses the abnormal (accessory) path way, which bypasses the AV node. This bypass tract (accessory pathway, AP) conducts faster than the AV node; therefore, a portion of the electrical current

MAT

reaches the ventricle sooner (the delta wave on the

Multifocal

atrial

tachycardia

(MAT)

mainly

diagnosed by ECG criteria of atrial rate > I 00 beats/ minute with P waves of at least 3 distinct morphologies. MAT is usually seen in patients with pulmonary disease and may be a result of theophylline use. MAT can also be caused by very low K+ and Mg+2. Therapy is directed at underlying illness. If medications are deemed necessary, calcium channel blockers or amiodarone might be useful. Digoxin is of no use in MAT! It can actually worsen it, in addition to causing digoxin-toxic arrhythmias.

ECG) and preexcites the ventricle-hence the alterna tive name, "preexcitation syndrome." Occasionally, the accessory pathway is concealed, and the delta wave is not visible. An unusual cause of WPW can involve Ebstein anomaly of the tricuspid valve. Spectrum of arrhythmias related to WPW includes orthodromic AVRT (narrow QRS complex regular tachycardia, which uses the AV node antegrade and AP retrograde), antidromic AVRT (wide QRS complex regular tachycardia, which uses the AP antegrade and AV node retrograde), and atrial fibrillation (irregularly irregular

wide

QRS

complex

tachycardia

using

antegrade AP conduction).

SVT

Treatment of accessory pathways: Many patients have

Supraventricular tachycardia (S VT) refers to narrow

completely asymptomatic AP and no dysrhythmias.

QRS

complex tachycardias

originating

above

the

ventricles. The key step in assessment is recognition of P wave and position of P wave in comparison to QRS.

Patients with AP and symptoms of tachycardia (called WPW syndrome) can be treated with vagal maneuvers, adenosine, or calcium channel blockers-same as any

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ARRHYTHMIAS

Ventricular Tachycardia ECG Findings Ventricular tachycardia (VT) is defined as 3 or more •

sequential QRS complexes of ventricular origin at a rate

How is the CHADS2 score calculated? At what

of 100 bpm or faster. Based on duration and association

CHADS2 score should you treat with warfarin/

with symptoms, VT can be defined as nonsustained

NOACs (unless contraindicated)?

(asymptomatic with duration of less than 30 seconds)

•

In what patient group is MAT found?

•

What is the treatment for acute A-fib in WPW?

•

On an ECG, PVCs are often followed by what

Monomorphic VT is generally regular in rate and

type of pause?

appearance. It needs to be differentiated from SVT with

•

or sustained (symptomatic or duration of more than 30 seconds). VT can be monomorphic and polymorphic.

aberrant conduction, bundle-branch block, pacing, and

Ventricular tachycardia (VT) is defined as ::: 3

QRS changes due to severe hyperkalemia. The majority

sequential PVCs occurring at what bpm? •

of patients with monomorphic VT have structural heart

List the ECG criteria consistent with VT.

disease (particularly ischemic heart disease). Idiopathic VT occurs in otherwise structurally normal hearts and

SVT! (In these cases, the impulses are moving down

has much better prognosis. The most common idiopathic

the normal conduction system and returning via the

VT is right ventricular outflow tract (RVOT) VT.

accessory pathway to complete the circuit.) But never treat acute A-fib in WPW with digoxin, verapamil, or beta-blockers. Although verapamil and

digoxin

increase the refractory period in the AV node, they can preferentially enhance conduction down the accessory pathway and precipitate ventricular fibrillation (V-fib ). Instead,

treat

acute

A-fib

WPW

with

procainamide, ibutilide, or amiodarone. Shock if there are any signs of hemodynamic deterioration in any WPW tachyarrhythmia; especially watch those with ventricular rate > 285 bpm because they are at greatest risk of V-fib. WPW syndrome is associated with a low but definitive risk of sudden death, and therefore radiofrequency ablation is the preferred long-term treatment option!

ECG criteria indicative of VT [Know!]: •

•

AV dissociation Fusion and capture beats Northwest axis Positive or negative concordance in precordial leads Absence of rS complex in all precordial leads If rS is present, r to S time > I 00 msec QRS width of > 140 msec with a RBBB QRS width > 160 msec with a L BBB

If a patient with a history of structural heart disease develops wide QRS complex regular tachycardia, VT is significantly more likely than SVT. VT also

can be bidirectional, with

the complexes

alternating in direction; this is usually due to digitalis

VENTRICULAR ARRHYTHMIAS

intoxication but also can be seen post-MI and in a rela tively rare genetic condition called catecholaminergic

PVCs

polymorphic ventricular tachycardia (CPVT).

Premature ventricular contractions (PVCs) often have

Polymorphic VT generally has irregular ventricular

a compensatory pause; that is, they do not reset the

rate and displays polymorphic QRS morphology. QRS

sinoatrial node, and the time between the sinus beats that

complexes appear to twist around an isoelectric axis.

are on either side of the PVC= 2 basic RR intervals. Asymptomatic, simple PVCs do not need to be treated if LV function is normal. If you do attempt treatment (beta-blockers are I 51 line), the PVCs should decrease by 80% for the treatment to be considered successful otherwise, stop treatment. (Most patients have spontane

Duration of polymorphic VT is typically brief; however, it can be sustained and can degenerate into V-fib. It can

(torsades de pointes) or in patients with normal QT interval (typi cally in the setting of ischemia/M1). occur in patients with prolonged QT interval

ous resolution, or decrease anyway.) Simple PVCs occur

Treatment

beyond the T wave, are uniform, and have constant cou

For sustained monomorphic VT, do the following:

pling (reentrant).

•

Complex PVCs (pairs, triplets) also do not need to be treated if the patient is asymptomatic and has no heart disease! If a patient has had an MI and has an ejection fraction of <

40%, frequent PVCs (> 10/hour) indicate a high risk of

sudden cardiac death-especially if they are sequential.

•

Stable: Give IV amiodarone. Hemodynamically compromised: Shock. Unstable and refractory to electrical cardioversion: Give IV amiodarone/procainamide.

•

VT specifically with acute MI: Most use amiodarone first. IV lidocaine can be useful.

5-43

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ARRHYTHMIAS

For

sustained

polymorphic

VT,

the

same

monomorphic, except: •

IV beta-blockers if ischemia is suspected or cannot be

•

IV amiodarone, as long as there is no prolonged QT

•

Urgent cath if ischemia is suspected

•

Assess for torsades de pointes (see below)

excluded

Never

use

verapamil

with

any

wide

tachycardias in the emergency setting.

(30%

•

Antibiotics (macrolides)

•

Antihistamines (astemizole and terfenadine)

•

Antifungal agents (ketoconazole)

You also can see TdP in association with very low K+ or Mg+2. Bradycardia can promote TdP in patients with prolonged QT.

complex

Treat torsades de pointes with:

of those •

with ventricular tachycardia rapidly deteriorate!)

•

RVOT VT can be terminated acutely with adenosine, and

Haloperidol and tricyclic antidepressants

•

beta-blockers/calcium channel blockers (CCBs)

can be used for long-term management. Remember, you

DC cardioversion for sustained episode. Magnesium sulfate 2--4 grams IV over 1 0-15 minutes.

•

Correction of hypokalemia.

generally do not want to use CCBs for wide-complex

•

Correction of bradycardia (isoproterenol or pacing).

tachycardias.

•

Never treat with Class Ia or Class III antiarrhythmic drugs (AADs).

To prevent recurrence of TdP:

Implantable Cardioverter-Defibrillators

Implantable cardioverter-defibrillators (ICDs) can be used for secondary (after event occurs) or primary prevention.

offending medications, isoproterenol

overdrive

discontinue any

prevent bradycardia with pacing,

potassium and magnesium.

supplement

The following are Class I indications for ICDs from the

2008

ACC/AHA device therapy guidelines and

focused update: •

2012

Patients who are survivors of cardiac arrest due to VF or who have hemodynamically unstable sustained VT after evaluation has excluded any completely Patients with structural heart disease and spontaneous sustained VT

(> 30

sec), whether hemodynamically

stable or unstable •

Patients with syncope of undetermined origin with VT or VF induced at electrophysiological study

days post-MI and are in the NYHA

indicate

with

heart

increased disease,

risk

for

particularly

death

ischemic

cardiomyopathy. NSVT patients are at risk of sustained VT and sudden death when:

•

they have ischemic cardiomyopathy (LVEF< 40%), or sustained VT can be induced at electrophysiologic

These patients benefit from lCD implantation.

Patients with nonischemic dilated cardiomyopathy

35%

40%,

have good prognosis, and they do not require further

and who are in the

PACEMAKERS

Patients with nonsustained VT due to prior MI, LVEF::;

and inducible VF or sustained VT at

electrophysiological study

type of polymorphic VT. It is associated with prolonged QT interval (congenital or acquired). Acquired forms are Drugs that commonly cause TdP are: Class Ia antiarrhythmic drugs (quinidine, procainamide, disopyramide) Class III antiarrhythmics (sotalol, dofetilide, and

pacing

indicated

for

patients

with

symptomatic bradycardia, sinus node dysfunction (sick sinus syndrome), and AV conduction problems. In the

Know this topic! Torsades de pointes (TdP) is a common

most often drug induced.

Permanent

absence of symptoms, permanent pacing should be

Torsades de Pointes

•

can

management.

(DCM) who have an LVEF::;

•

patients

Patients with NSVT without structural heart disease

NYHA functional Class II or III •

PVCs with HR

functional Class II or III; also, LVEF< 30% and in

the NYHA functional Class I •

(> 3 sequential 30 seconds.

bpm) lasting for<

testing (EPT).

Patients with LVEF::; 35% due to prior MI who are at least

as asymptomatic VT

> 100

•

clinically relevant, hemodynamically significant sustained

•

Nonsustained ventricular tachycardia (NSVT) is defined

NSVT

reversible causes •

Nonsustained Ventricular Tachycardia

strongly considered for patients with complete heart block and advanced (i.e., not Wenckebach) type 2 second degree AV block (particularly associated with wide QRS). The most common pacemaker (Table

5-12)

is DOD,

which stands for dual-chamber paced, dual-chamber sensed, and dual response to sensing: triggered and inhibited. Most clinicians use DDD, unless the patient is in chronic, slow atrial fibrillation. The DDD is the most physiologic and provides better exercise tolerance.

amiodarone)

ARRHYTHMIAS

•

Mexiletine is effective in most patients who respond to lidocaine.

•

Digoxin works by inhibiting membrane ATPase. It increases contractility and slows AV conduction

•

With what type of tachycardia should you never use verapamil?

•

ICDs are recommended for primary prevention in what situations with ischemic and

Quinidine increases digitalis levels.

Class 1: Sodium channel blockers that slow electrical

conduction in the heart.

nonischemic cardiomyopathy patients? •

and HR. •

Ia:

Which antiarrhythmic drugs prolong the

Quinidine,

procainamide,

disopyramide-slow

conduction velocity, prolongs action potential duration,

QT interval?

and can prolong QT interval.

•

What is the treatment for torsades de pointes?

•

Under what conditions is permanent pacing

action potential duration slightly with no significant QT

recommended?

prolongation.

How long do you have to wait for an

lc: Flecainide and propafenone-slow conduction veloc

antiarrhythmic to reach steady-state

ity without effect on potential duration or QT interval.

•

therapeutic levels?

lb: Lidocaine, tocainide, mexiletine, phenytoin-shorten

Class II: Beta-blockers-decrease heart rate and blood

"Pacemaker syndrome" (associated lightheadedness and/ or syncope) can occur with single-chamber ventricular pacing and is commonly cured by dual-chamber (DDD) pacers, which restore the atrial "kick." "Pacemaker-mediated tachycardia" can occur when paced ventricular complexes are sensed by the atrial lead and then trigger subsequent ventricular paced beats; this cycle can continue indefinitely.

pressure by blocking impulses that can cause irregular heart rhythm and decreasing hormonal effects (e.g., adrenaline) on the heart. Class Ill: Amiodarone, sotalol, and the newer agents,

dofetilide (oral Tikosyn®) and dronedarone (Multaq®} prolong the action

potential by potassium channel

blockade. These agents can cause QT prolongation. Note: See side effects on dronedarone below. Class IV: Calcium channel blockers, especially vera

pamil and diltiazem, slow inward current. They decrease

ANTIARRHYTHMIC THERAPY

heart rate and blood pressure like class II.

Drugs Adenosine and Digoxin

Overview

With antiarrhythmic drugs (AADs), always wait 4--5 half-lives before determining whether a drug is effective. Notes:

Digoxin is not in the above classes of antiarrhythmics, but it has antiarrhythmic effects and occasionally is used for this. Remember that digoxin is usually reserved for treating severe heart failure.

•

All AADs have a proarrhythmic potential.

Adenosine is also not in the above groups. Adenosine

•

Per the CAST study, there is evidence that Ic

slows conduction in the AV node and is used for

anti-arrhythmic drugs decrease survival in patients

conversion of S VT (AV node reentry) to normal sinus

with ventricular arrhythmias that occur post-MI. The

rhythm. It also induces coronary artery vasodilation and

only drug that shows a benefit is a beta-blocker after a

is used in cardiac perfusion imaging. It depresses LV

Q wave (ST elevation) infarction.

function, but it has such a short half-life, it can even be used in patients with decreased LV function.

Table 5-12: Permanent Pacemakers The North American Society of Pacing and Electrophysiology/British Pacing and Electrophysiology Group (NBG) Code First letter= chamber(s) paced-VIAID (ventricle, atrium, or dual [V +A]) Second letter= chamber(s) sensed-V/A/D/0 (ventricle, atrium, dual [V +A], or none) Third letter= mode(s) of response---T - /1/D/0 (triggered, inhibited, dual[!+ I], or none) Fourth letter= programmability-P/M/C/R/0 (programmable rate and output, multiprogrammable, communicating, rate-modulated, or none) Fifth letter= arrhythmia control-P/S/D/0 (pacing, shock, dual[P + S], or none)

5-45

5-46

ARRHYTHMIAS

Notes on Verapamil

Class Ill: All of them can cause prolonged QT, QRS,

Avoid verapamil with:

and torsades de pointes.

•Atrial fibrillation or atrial flutter occurring in WPW •Wide-complex tachycardias •Beta-blockers-relative contraindication because they are both negative chronotropes and negative inotropes •Patients with asymptomatic hypertrophic

• Amiodarone is the most effective, but also, due to the extremely high iodine content, it is the most toxic antiarrhythmic drug. It causes corneal deposits in 98% of patients!-also, hyper/hypothyroidism, pulmonary fibrosis, gray skin, and sun sensitivity but not hematologic changes. Pulmonary fibrosis

cardiomyopathy (HCM)

from amiodarone can be severe and is fatal 10%

•Patients with obstructive HCM in the setting of

of the time. It ordinarily occurs in the first year of

systemic hypotension or severe dyspnea at rest

treatment. It tends to occur only in older patients

(> 40 years old),

Okay to use verapamil: •To control the ventricular response to A-fib or atrial flutter in an otherwise healthy heart

and in those with low CO dif

fusing capacity. (Pulmonary fibrosis is unlikely to develop on a maintenance dosage of< 200 mg/day.) Amiodarone also causes a less common acute form

•MAT

of pulmonary toxicity. Again, amiodarone: hepatic

•SVT (2"d choice after adenosine)

toxicity; extremely long half-life (40-55 days);

•Symptomatic treatment in HCM (but look above

hyper/hypothyroidism; gray skin.

regarding avoiding verapamil in HCM)

• Dronedarone: July 2011-dronedarone showed 2x increased mortality in patients with permanent

•Severe, concentric LVH

A-fib and class III and IV heart failure. Current

•Hypertension

recommendation is to not prescribe dronedarone to patients with permanent A-fib.

Major Side Effects of AADs [Know!] All AADs are, by their nature, arrhythmogenic. Especially remember the following:

• Dofetilide: works by blocking the cardiac ion channel carrying the delayed rectifier potassium current (IKr) . It is used to treat highly symptomatic A-fib and can be used in patients with CAD and

Class Ia: • Quinidine: prolongs the QRS complex and the QT interval--occasionally leading to torsades de pointes, diarrhea, and (rarely) autoimmune thrombocytopenic purpura. Also "cinchonism": hearing loss, tinnitus, and psychosis.

HF. Dofetilide must be started as an inpatient by approved prescribers and is renally-dosed. It can cause significant Q T prolongation requiring dose reduction or discontinuation. Do not use dofetilide with the following medications: cimetidine, vera pamil, ketoconazole, trimethoprim, prochlorperazine,

• Procainamide: Prolongs QT and QRS but also

megestrol, or any form of hydrochlorothiazide; these

causes blood dyscrasias, such as agranulocytosis,

agents can increase the activity of the CYP3A4 liver

neutropenia, and thrombocytopenia, in - 0.5%. It also causes drug-induced lupus and must be used

enzyme and increase dofetilide levels. Digitalis toxicity is more likely to occur in elderly

with caution in HF patients because it has a mild

patients and in those with low K+, low Mg+2, or low

myocardial depressive effect. • Disopyramide: prolonged QT, QRS, and torsades de

pointes. It is also anticholinergic and vagolytic, so it causes urinary retention, constipation, dry mouth, and negative inotropic effects. Because quinidine

p02 (low, low, low), and impaired renal function. The toxic levels of digoxin are determined by changes in the ECG, not by blood levels. Most common ECG changes are bradycardia and prolonged PR interval.

and disopyramide prolong both the QRS and QT intervals, avoid them in patients with 2nd or 3'd degree heart block. Disopyramide has a negative inotropic effect, so avoid in patients with HF.

Electrophysiologic Testing Electrophysiologic (EP) studies are most commonly used to identity and characterize SVTs and VTs, often as

Class lb:

a precursor to radiofrequency ablation.

•Lidocaine: seizures. •Tocainide is now used less often because of an

Radiofrequency Ablation

association with aplastic anemia.

Radiofrequency ablation is the treatment of choice for

Class II: Beta-blockers commonly cause decreased libido and impotence. They must be tapered slowly; stopping a beta-blocker abruptly can precipitate angina.

WPW syndrome. It is also used for the following if the patient prefers it to standard drug therapy or the condition is not responsive to meds: •AVNRT •Atrial tachycardia

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SYNCOPE

MI within 3 months and TIA/CVA within 3 months. Relative contraindications to CSM include previous

Q..• trk...

u--·'-!uiz

•

VTNF or carotid bruit.

When is it okay to use verapamil; when is it not okay?

•

Which antiarrhythmic drug can cause lupus?

•

Name the side effects associated with

•

Orthostatic hypotension: Syncope due to orthostatic hypotension 2° autonomic dysfunction causes symptoms with no increase in the patient's heart rate with standing or during the vertical phase of tilt-table testing.

amiodarone. •

Arrhythmia: Bradycardia, SVT, or VT.

Typically,

What determines a toxic level of digoxin? For what conditions is the treatment of choice radiofrequency ablation, guided by EP studies?

try nonpharmacologic therapy first (e.g.,

support hose and increased salt); but treatment can also include midodrine (ProAmatine®). Midodrine is a prodrug for desglymidodrine, an alpha agonist that stim ulates the alpha-adrenergic receptors of both arteriolar

•

What is the most common cause of syncope?

•

Explain how you approach the diagnostic

agonist that promotes retention of sodium and water,

workup in a patient with probable

also can be used but can cause supine hypertension.

neurocardiogenic (vasovagal) syncope. •

and venous vessels. Fludrocortisone, a mineralocorticoid

Organic heart disease: Anatomic causes include

What are the tests used to work up high-risk

depressed EF

(causing VTNF),

patients with syncope?

myxoma, PE,

pulmonary

AS,

HCM,

atrial

hypertension (HTN), and

ischemia. •

Atrial flutter

Medications: Check the patient's history for new

•

Idiopathic VT

medications.

It has also been used to treat atrial fibrillation by ablating a focal source of A-fib or by destroying the AV node and placing a ventricular pacemaker.

Common

syncope include

medications

cardiovascular,

associated

with

neurologic, antipar

kinsonian, and antidepressants. A classic cause of drug-related syncope includes medications for BPH (prazosin, terazosin, and tamsulosin). A thorough history, physical exam, supine and upright

SYNCOPE

blood pressure, and ECG are an essential part of the ini tial evaluation followed by additional testing in selected

Syncope is sudden transient loss of consciousness with associated loss of postural tone and spontaneous recovery. It is important to differentiate syncope from other types of loss of consciousness. Classifications of syncope:

Neurally mediated (reflex) syncope symptoms include dizziness, lightheadedness, and fatigue, with prodro mal features such as diaphoresis, pallor, palpitations, nausea,

hyperventilation,

and

yawning.

Myoclonic

subgroups (carotid sinus massage, echocardiogram). If the diagnosis is certain, treatment is initiated. If the diag nosis remains uncertain, stratify the patient to determine whether the patient is at increased risk of death (typically patients with severe structural heart disease, clinical, or ECG features suggesting arrhythmic syncope). High-risk

patients

should

admitted

for

further

workup, which can include coronary angiogram and EP study. Low-risk patients, particularly with only I episode

jerks can occur when the patient is unconscious, and

of syncope, usually do not require further evaluation.

it needs to be distinguished from seizure activity.

If the history is typical, and this is the first episode in

Several subtypes: •

Vasovagal syncope, as in the common faint, is the most common cause of syncope. It is triggered by

Initial measures aimed

intense emotion, pain, prolonged standing, alcohol, or heat exposure. Vasovagal episodes are typically preceded by a prodrome that includes nausea, vomit ing, flushing, hot flashes, and diaphoresis. Extremely elderly patients may not have a classic prodrome. •

•

a young patient with no suspected heart disease, the patient can be reassured and sent home. at reducing events include

avoidance of precipitating factors and also avoiding volume depletion. Patients should also be taught to sit or lie down at the onset of symptoms and to initiate physi cal isometric maneuvers (leg crossing and hand grip). Value of pharmacologic agents (beta-blockers, fludro

Situational reflex syncope is triggered by cough,

cortisone, midodrine) is less certain. Frequent episodes,

micturition, etc. These triggers provoke reflex

despite initial management, require evaluation with con

vasodilation and bradycardia leading to syncope.

tinuous ambulatory electrocardiography (patients with

Carotid sinus hypersensitivity may be responsible for

severe cardioinhibitory response during syncope could

up to 40% of falls in the elderly and is diagnosed with

benefit from pacemaker placement). Patients in high

a pause > 3 seconds during carotid sinus massage

risk occupations should be investigated with the first

(CSM). Absolute contraindications to CSM include

episode of syncope.

5-47

5-48

CARDIOMYOPATHIES

Approximately 1/4 of patients with HCM have a resting

CARDIOMYOPATHIES

gradient (greater than 30 mmHg).

There are 3 main types of nonischemic cardiomyopathy:

A majority of patients with HCM have normal life

hypertrophic, restrictive, and dilated.

expectancy with little or no disability; however, subgroups of patients are at risk for complications, including sudden death, progressive heart failure, and atrial fibrillation.

HYPERTROPHIC CARDIOMYOPATHY Hypertrophic common

cardiomyopathy the

genetic

(HCM)

the most

cardiovascular

diseases

Risk factors for sudden death in HCM (and possible role for ICDs): •

Septal thickness

[Image 5-11]). It is characterized by a thickened but not

•

Personal history of syncope

dilated left ventricle in the absence of other cardiac or

•

Family history of sudden death in I st degree

•

NSVT on Holter monitor

•

Failure to augment systolic BP on exercise tolerance

(autosomal

dominant

pattern

inheritance;

systemic conditions (HTN, aortic valve stenosis). HCM is the most common cause of sudden death in young age (age < 35), including competitive athletes.

30 mm

family member

Patients with HCM typically present with heart failure,

testing (< 10 mmHg increase at peak exercise)

chest pain (typical or atypical), or syncope. They can be asymptomatic and recognized because of abnormal physical exam (murmur). Bedside with HCM: The patient typically has a harsh, crescendo-decrescendo systolic murmur, typically in

Treatment for HCM Treatment for HCM: •

the left yct space, which increases with Valsalva and

diastolic filling by slowing heart rate.

decreases with sustained handgrip. There is a carotid pulse that has a brisk upstroke, but, because outflow

•

symptom control. •

phenylephrine (or other pure vasoconstrictor) is

recommended for treating acute hypotension in HCM

can surprise you with a double- or triple-tap impulse.

patients who do not respond to IV fluids.

A mitral regurgitation murmur can also be heard from systolic anterior motion (SAM) of the mitral valve due

Disopyramide with beta-blockers for obstructive HCM when other drugs fail to achieve

obstruction occurs late in systole, it is bifid in 2/3 of HCM patients. The briskness of the upstroke further distinguishes it from aortic stenosis. Palpation at the apex

Beta-blockers (obstructive and nonobstructive HCM) and verapamil (obstructive HCM) improve

•

to a suction-like effect of the outflow obstruction.

lCD placement is recommended for HCM patients with prior documented cardiac arrest, ventricular fibrillation, or hemodynamically significant VT.

The ECG with HCM is abnormal in more than 90%

lCD is also reasonable to place if sudden cardiac

of patients. Most common abnormalities include LVH,

death (SCD) in 2: 1 first-degree relative(s), LV

ST-T changes with sometimes marked T wave inversion

wall thickness 2: 30 mm, or 2: 1 recent unexplained

in the lateral precordial leads, and Q waves in inferior

syncopal episode(s).

and lateral leads. Diagnosis is commonly made with echocardiogram,

•

Septal reduction therapy via intracoronary injection of ethanol to cause a controlled septal infarction can

although recently cardiac MRI has emerged as a new

reduce the obstruction in eligible patients with severe

diagnostic modality. There is no single classic mor

drug refractory symptoms and left ventricular outflow

phologic form, and virtually all possible patterns of

tract (LVOT) obstruction. Diuretics with beta-blockers

hypertrophy have been described. Some patients have

to reduce filling pressures in hypertrophic cardiomy

dynamic obstruction related to SAM of the mitral valve.

opathy (HCM) patients with severe heart failure, and then only with extreme caution! •

Septal myectomy is preferred treatment for patients with severe drug refractory heart failure (HF) symptoms (NYHA III and IV).

RESTRICTIVE CARDIOMYOPATHY Restrictive cardiomyopathy must be differentiated from constrictive pericarditis (page 5-55) because the signs and symptoms can be similar. Although constrictive pericarditis is often quickly treated with good results, restrictive cardiomyopathy is not reversible. Arrhythmias, such as atrial fibrillation, occur early in the course of these diseases. Constrictive pericarditis is a pericardia! problem; restrictive cardiomyopathy is a myocardial problem.

image 5-11: Hypertrophic cardiomyopathy

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HEART FAILURE

•

Q�uiz •

Organic solvents ("glue sniffers" heart) L ate hemochromatosis

American countries. In

What are the 3 main medications used in the

contrast,

nonischemic

cardiomyopathies

include

cardiomyopathies due to volume or pressure overload,

treatment of HCM? •

•

Think Chagas disease in patients from Central and South

What are the risk factors for sudden death in patients with HCM?

•

Catecholamines

such as hypertension or valvular heart disease.

What are some causes of restrictive

In pregnant women, a peripartum cardiomyopathy can

cardiomyopathy?

occur anytime from the beginning of the last trimester

•

List some of the etiologies of DCM.

•

In the 2013 ACC/AHA, what are the newly

through the first 6 months postpartum. Heart failure due to dilated cardiomyopathy is treated

defined 2 major subdivisions of heart failure?

similarly to other causes of HF (see below).

Causes of restrictive cardiomyopathy include amyloi dosis, sarcoidosis, hemochromatosis, and lipid storage

HEART FAILURE

diseases. On 20 echocardiogram, the myocardium may be thickened with a granularity, which suggests an infiltrative process. Thoracotomy is occasionally done to ensure that you do not miss a treatable constrictive pericarditis; these are treated with pericardiectomy.

OVERVIEW Heart failure (HF ) is defined as a complex clinical

syndrome resulting from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Left ventricular ejection frac

Treat mild-to-moderate restrictive cardiomyopathy with

tion (LVEF ) is considered important in classification of

diuretics.

patients with HF.

DILATED AND NONISCHEMIC

Americans :::0: 40 years of age. African-American males

CARDIOMYOPATHIES

have the highest risk for HF, and the highest 5-year mor

The lifetime

Patients with dilated

cardiomyopathy

risk

developing

20%

for

tality rate (Atherosclerosis Risk in Communities [ARIC] (DCM)

have

ventricular dilation and depressed myocardial contractility in the absence of abnormal loading conditions such as hypertension or valvular disease. African-Americans have

Study-ongoing). The 2013 ACC/AHA definitions: •

to Caucasians.

Heart failure with reduced ejection fraction (HF rEF): EF :::; 40%, systolic HF

nearly a 3-fold risk for developing DCM when compared •

Heart failure with preserved ejection fraction (HFpEF): EF :::0: 50%, diastolic HF

The prognosis of patients with symptomatic HF and DCM is poor, with 50% mortality at 5 years.

Cardiac output is well maintained in mild HF, usually

Etiologies of DCM:

at the expense of increased left ventricular end-diastolic

•

Familial cardiomyopathies (e.g., noncompaction)

•

Idiopathic (probably viral-most common)

•

Obesity

•

Diabetes

•

Hyperthyroidism

•

Acromegaly

•

Alcohol

•

Cocaine

•

Cancer chemotherapy (especially anthracyclines)

volume (LVEDV) and increased heart rate. Numerous

adaptations

occur

response

heart

failure in the peripheral circulation, kidney, skeletal muscle, and other organs. The changes contribute to the overall clinical manifestations and ultimately become maladaptive. In

response

exercise,

LVEDV

and

plasma

norepinephrine rise more than in controls, but the resulting

cardiac output increase

does not rise in

proportion to 02 consumption-so the patient has

•

Ephedra

dyspnea

•

Cobalt

adrenergic system and the renin-angiotensin-aldosterone

•

Anabolic steroids

•

Chloroquine

•

Clozapine

•

Amphetamines

•

Methylphenidate

MedStudy

exertion

and is

easily

fatigued. The

system play a major role in progression of heart failure and maladaptive mechanisms.

5-49

5-50

HEART FAILURE

Stage C HF patients have structural heart disease

LOW-OUTPUT HF

with prior or current symptoms of heart failure. These

NYHA Classification

are patients with structural heart disease as described

NYHA (New York Heart Association) classification

above in Stage B, and who additionally have signs and

of heart failure (classes and definitions) is a functional

symptoms of HF (e.g., dyspnea, fatigue, and decreased

classification based on how much the patient is limited

exercise tolerance).

during physical activity. In clinical use, it is being superseded by the ACC/AHA classification

(next).

NYHA classification:

Goals for Stage C therapy are control symptoms, patient education, improved health-related quality of life, and prevention of hospitalization and mortality.

Class 1: Cardiac disease but no limitation in physical activity. Class II: Slight limitation of normal physical activity

Stage C drugs are: •

loop diuretics for all volume overload NYHA II-IV patients, hydralazine/isosorbide dinitrate

(fatigue, palpitations, dyspnea, and/or angina).

for symptomatic African-American NYHA III-IV

Class III: Marked limitation of physical activity. Slight

patients, aldosterone antagonist for NYHA II-IV

activity causes symptoms.

patients (Cr

Class IV: Symptoms may be present at rest. Unable to

•

30 mL/min and K < 5 mEq/dL), and

statins and beta-blockers as used in Stage B (i.e., if

MilACS), and ACEis/ARBs as used in Stage A.

carry on any physical activity without discomfort.

Use

lCD

and/or cardiac resynchronization therapy

(CRT) if indicated, and revascularization or vascular

ACC I AHA Staging The 2013 ACCIAHA staging system for HF shows heart failure as more of a progressive disorder and has goals of therapy for each stage (A through D). Know the defi nition, goal of therapy, and medications for each stage

surgery as appropriate.

Stage D HF patients have marked symptoms at rest and frequent hospitalizations despite maximal medical therapy.

of HF.

Goals for Stage D therapy are to control symptoms,

Stage A HF patients are at high risk for heart failure but

improve health-related quality of life, reduce hospital

have no structural heart disease/symptoms of HF and

readmissions, and establish patient's end-of-life goals.

include those with hypertension (HTN), atherosclerotic

Stage D drugs are the same as those for Stage C.

disease, diabetes, obesity, and metabolic syndrome. Stage A also includes any asymptomatic patient using cardiotoxins (such as anthracycline) or with a family history of cardiomyopathy. So yes, you read this right: Just having HTN means you have Stage A heart failure!

Options for Stage D patients also include consideration of "extraordinary measures," including heart transplant, chronic inotropes, temporary or permanent mechanical circulatory

(HTN, lipid disorder) and control/avoid other condi tions that can lead to or contribute to HF, such as obesity, diabetes mellitus, tobacco use, and known cardiotoxic agents (excess alcohol/illicit drug use). Regular physical activity to improve functional status is recommended in all HF patients. Stage A drugs include ACEis/ARBs/statins in appropriate patients.

assist

devices),

and

Until definitive

is performed or acute precipitating problem resolves, patients with cardiogenic shock should receive tempo rary IV inotropic support to maintain systemic perfusion and preserve end-organ performance. The most common causes of HF with reduced EF (HFrEF) are: •

without signs or symptoms of heart failure. This stage includes patients who have a history of a previous MI and those with LV remodeling from left ventricular and those with

asymptomatic valvular heart disease.

therapy (coronary revascularization,

mechanical circulatory support, or heart transplantation)

Stage 8 HF patients have structural heart disease but

or low LVEF,

(ventricular

care, hospice, and lCD deactivation.

Goals for Stage A therapy are to treat the disorder

hypertrophy (LVH)

support

experimental surgery or experimental drugs; and palliative

coronary artery disease (40%-although recent data pushes this to near 60% of etiologies),

•

dilated cardiomyopathy (30%),

•

valvular disease (15%), and

•

hypertension (10%).

HF is the most common diagnosis in hospitalized elderly

Goals of Stage B therapy are to prevent HF symptoms and prevent further cardiac remodeling.

patients. Only 50% of patients with HF die from actual pump failure; - 40% die from arrhythmias!

Stage B drugs are: ACEis/ ARBs, beta-blockers, and statins if history of Mil ACS. Use lCD if indicated, and revascularization or vascular surgery as appropriate.

HEART FAILURE

•

,.------•

Define Stage A through Stage D heart failure

LV dysfunction

(ACC/AHA classification). What are the goals of therapy for each of these stages? •

•

Deer BP/Decr Renal perfusion

What is the sequence of drugs used to treat HF based on ACC/AHA stages?

Na and H,O retention

What are the most common causes of

Vasoconstriction

!ncr sympathetic tone !ncr renin-angiotensin I ncr vasopressin

low-output HF? •

Adapted from Califf . NEJM 330(24): 1724-30

What factors are associated with poor prognosis in HF?

•

Figure 5-6: Sptral of Worsentng HF

What is the sequence of events that worsens HF?

Let's see if we have all of that: Low CO perfusion

Determining Prognosis in HF In severe HF, a worse prognosis is associated with:

-->

high renin

-->

low renal

�

high

angiotensin II --> high aldosterone --> retentton of Na + --> retention of water --> high filling pressure --> exacerbation of HF (Figure

•Lower ejection fraction

-->

high angiotensin I

5-6).

The increased heart

rate in HF is due to both an increased sympathetic tone

•Low sodium

and an increased level of catecholamines in an attempt

•CKD

to compensate for reduced stroke volume. The higher

• Anemia

the catecholamine pool, the worse the prognosis.

• Elevated troponin

ADH is released from

•High brain natriuretic peptide (BNP)

the

hypothalamus but has

a minor effect.

•Increased width ofQRS

�

•Persistent sinus tachycardia •Poor functional capacity (NYHA III and I V) • High norepinephrine and catecholamine levels

Atrial (or A-type) natriuretic peptide (ANP) and bra n _ natriuretic peptide ([BNP]; also called B-type natnurettc peptide) are released from the heart myocytes; the release is stimulated by stretching of the atrium (ANP and BNP)

Exercise training in patients with stable chronic HF is

and the ventricle (BNP). ANP and BNP increase excre

associated with an II% reduction in combined all-cause

tion of sodium and water, cause vasodilation, and inhibit

death or hospitalization (2009 HF-ACTlON Trial).

the effects of aldosterone. These peptides are released in

The Seattle Heart Failure Model and/or The Heart Failure

Survival

Score

can

provide

reasonable

an attempt to offset the effects of renin angiotensin and ADH but cannot antagonize them adequately.

"ballpark" estimate of HF prognosis based on standard

clinical data.

20-100-fold. High levels of these peptides (especially

severe

heart

failure,

the

BNP

increases

BNP) actually correlate directly with a poor prognosis in

Mechanism of HF Heart failure with reduced ejection fraction (HFrEF) results in decreased cardiac output. This in tum causes an increased A-a 02 difference and decreased renal perfusion. The decreased cardiac output can be due to systolic dysfunction, diastolic dysfunction, or both. Note that diastolic dysfunction can occur with normal cardiac output (see below). After a certain point, decreased car diac output from any type of HF causes decreased renal perfusion. This stimulates the release of renin, which _ allows the conversion of angiotensinogen to angiO tensin I. Angiotensin I is converted to angiotensin II in the lungs. Angiotensin II then stimulates the secre tion of aldosterone, which then causes retention of Na+ and water, causing a greatly increased filling pressure (moving the Starling curve to the right).

HF. BNP is also elevated in restrictive cardiomyopathy but not constrictive pericarditis and is used to differentiate between these disorders. About 50% of HFs are caused by diastolic dysfunction

�

(more recently termed "heart failure wit preserved E "; HFpEF) rather than systolic dysfunctton. Myo �ardt�l ischemia, severe concentric LYH, HCM, and dtabettc cardiomyopathy cause diastolic dysfunction, at least initially. With diastolic dysfunction, the CO is often normal; HF develops from increased filling �ressure (from decreased relaxation due to increased sttffne �s). So the problem is not that the ventricle is not squeezmg _ enough, but rather that it is not relaxing enough. Thts ts reflected in elevated left and right end-diastolic pressure (LVEDP and RVEDP), tachycardia, and an S4.

5-51

5-52

HEART FAILURE

Treatment for HF

•

General Measures

•

See above for treatment according to ACC/AHA stage. We will now discuss the individual drugs and how they affect/improve survival in heart failure. (Note: In our discussion, the term class refers to NYHA classification; the term stage refers to the ACC/AHA

Telmisartan (Micardis®)

*Randomized

controlled

trial

data

show

mortality

benefit in heart failure. Beta-Blockers

Beta-blockers are now part of standard heart failure

classification.) Current

•

Eprosartan (Teveten®) L osartan (Cozaar®)

pharmacologic

management

low-output

heart failure is aimed at reducing ventricular preload and afterload as well as diminishing, inhibiting, and/or antagonizing neurohormonal vasoconstrictor activation, rather than directly increasing cardiac contractility as in the past.

treatment. In HF, the sympathetic nervous system is overstimulated. This raises norepinephrine levels, which can cause cardiac remodeling, lead to arrhythmias, and increase mortality risk. Mortality is clearly improved by carvedilol

(

�

65%

relative risk reduction), metoprolol

succinate, and bisoprolol

( 35%). �

They are indicated in

patients with HFrEF and current or prior symptoms to

The optimal treatment of heart failure aggressively addresses the major risk factors including hypertension, diabetes, obesity, metabolic syndrome, hyperlipidemia, and coronary artery disease (CAD). Therapies that promote regression ofLV H or reverse remodeling of the dilated heart should be used; these include inhibitors of catecholamines and the renin-angiotensin-aldosterone pathway.

reduce morbidity and mortality. Previously, it was taught that starting these drugs while patients are decompensated is contraindicated. Current guidelines recommend initiation of beta blockade at any stage of heart failure, once adequate diuresis has been achieved and intravenous diuretics have been discontin ued. Carvedilol (Coreg®) is a nonselective beta-blocker that also has some alpha-blocker effect. Use in conjunction with ACE inhibitors in Class I-IV heart failure.

ACE Inhibitors and ARBs

Angiotensin-converting captopril,

enalapril,

enzyme inhibitors lisinopril,

([ACEis];

benazepril,

fosino

pril, quinapril, ramipril) are 1st line therapy. They are indicated in patients with HFrEF and current or prior symptoms to reduce morbidity and mortality. They decrease

systemic

vascular

resistance,

pulmonary

capillary wedge pressure, right atrial pressure, and

Diuretics

Give

diuretics

needed

for

volume control (i.e.,

decrease edema and pulmonary congestion) during Stage C therapy. Remember: Therapy now begins with ACEIs/ ARBs and beta-blockers before patients even have symptoms.

end-diastolic and end-systolic dimensions; and they

Diuretics

improve cardiac performance, as evidenced by increased

reduced or preserved EF for symptom control (volume

are

effective

both heart

failure

with

cardiac output and stroke volume, and by improved

overload). All but the aldosterone antagonist diuret

fractional shortening, as determined by echocardiogra

ics have no mortality benefit, unlike ACEis/ ARBs and

phy. Hence, they decrease tachycardia due to HF. ACEis

beta-blockers.

block formation of angiotensin II. They also decrease

Treat heart failure (HF) patients admitted with signifi

the incidence of ventricular arrhythmia and prolong survival. In addition, they reverse the remodeling in the

cant fluid overload promptly with IV loop diuretics. In those already receiving outpatient loop diuretics, the

myocytes, which causes progression of heart failure.

initial IV dose should be

Angiotensin II receptor blockers (ARBs) block the effect

and be given as either intermittent boluses or continu

of angiotensin II at the cell wall. ARBs are given in place of ACEis (if ACEI intolerant) and are equally effective

their chronic oral daily dose

ous infusion. Adjust diuretic dose for symptom relief, to reduce volume, and avoid hypotension.

(commonly grouped as "ACEVARB").

If a loop diuretic given twice daily in doses equivalent

ARBs cause less cough than ACEis and are often given

to furosemide

when patients develop refractory cough on ACEis. Cough

diuretic or metolazone can be added, which results in a

is caused by excessive bradykinin.

synergistic effect. This combination can result in severe

Monitor patients on ACEis/ARBs for renal impairment and hyperkalemia. Commonly used ARBs: •

Candesartan (Atacand®)*

•

Valsartan (Diovan®)*

•

Irbesartan (Avapro®)

•

Olmesartan (Benicar®)

100-200

mg/d is inadequate, a thiazide

hypokalemia, so close monitoring is necessary. Aldosterone

antagonists

(aka

mineralocorticoid

antagonists) reduce morbidity and prolong survival in NYHA II-IV and with reduced EF •

Spironolactone showed a

35%:

30% decrease in mortality

at 24 months when given to patients with Class IV HF or Class III having had Class IV in the previous

6 months ( 1999

RALES trial).

HEART FAILURE

•

When are beta-blockers started in the treatment

the baroreceptors and dampen the renin-angiotensin effects; it has very little inotropic effect. It also is used to control the ventricular rate in a patient with HF and atrial fibrillation. Digoxin has no mortality benefit. See Table 5-13 for Drugs that Increase Digoxin Level.

ofHF? •

With what type of HF do aldosterone antagonists prolong survival?

•

True or false? Digoxin can be beneficial in HFrEF patients to decrease hospitalizations forHF.

•

In what population is hydralazine

isosorbide

dinitrate beneficial? •

Which patients with chronic HF should receive anticoagulation?

•

Eplerenone showed a 15% decrease in mortality at 16 months in patients with recent Ml and EF < 40% and evidence of HF or diabetes mellitus (2003 EPHESUS trial). Monitor patients closely for hyperkalemia. NYHA II patients should have prior HF hospitalization and elevated plasma natriuretic peptides before being placed on aldosterone antagonists.

More notes on diuretics: •

•

Thiazides mainly block Na+ and Cl- resorption in the

distal convoluted tubule and, to a minor extent, block Na+ resorption in the proximal tubule. Examples are hydrochlorothiazide and metolazone (Zaroxolyn®). Spironolactone competitively inhibits aldosterone (so, is K+ sparing) and is being used increasingly in the management of chronic heart failure. Eplerenone is similar to spironolactone but more selective for the mineralocorticoid receptor. Furosemide (Lasix®), bumetanide (Bumex®), torsemide (Demadex®), and ethacrynic acid are the loop diuretics. They block Na+ resorption in the ascending limb of the loop of Henle. Bumetanide may also have some action on the proximal tubule. lndapamide (Lozol®, Lozide®) has an unknown mechanism of action. It has an antihypertensive effect occurring far below the antidiuretic effect. Probably has renal and extrarenal effects. Triamterene has an unknown mechanism of action.

With azotemia, do not use spironolactone or triamterene because these can cause hyperkalemia; thiazides are not effective, but furosemide usually is. Much more on this in Nephrology, Book 2.

Nitrates

Nitrates are occasionally used next (good venodilator, moderate arterial dilator}-remember the nightly 6-hour nitrate-free window to prevent tolerance (discussed under Anti-Anginal Drugs on page 5-12). With ventricular failure, patients can have increased systemic (peripheral) vascular resistance (SVR) with a normal or low BP, and they still benefit from an arteriolar vasodilator. Hydralazine and lsosorbide Dinitrate

Hydralazine is an afterload reducer (arterial vasodilator); it also increases heart rate. Hydralazine is fre quently used with nitrates to get the added benefit of decreased preload. The combination of hydralazine and isosorbide dinitrate is recommended to reduce morbidity and mortality in African-Americans with NYHA III-IV HFrEF, as adjunctive therapy to ACEis (or ARBs) and beta-blockers (2004 A-HeFT). The combination can also be helpful in patients with current or prior symp tomatic HFrEF who cannot be given ACEIs/ARBs (drug intolerance, hypotension, renal insufficiency). Anticoagulation

For patients with chronic HF and permanent, persistent, or paroxysmal atrial fibrillation plus an additional risk factor for cardioembolic stroke (Hx HTN, DM, previous stroke/TIA, or age 2': 75) give individualized anticoagu lation (warfarin, dabigatran, apixaban, or rivaroxaban).

Table 5-13: Drugs that Increase D1goxm Level Alprazolam Amiodarone Abx: Macrolides and tetracycline Cyclosp�Min� Diphenoxylate or propantheline (decrease bowel motility) Indomethacin

..�

Itraconazole (antifungal) Digoxin

Omeprazole

Digoxin can be beneficial in HF with reduced EF to decrease hospitalizations for HF. It is started after the above therapies are established and the patient is still symptomatic. In HF, digoxin appears to reset

Propafenone (class Ic antiarrhythmic)

MedStudy

Quinin� Spironolactone

5-53

5-54

HEART FAILURE

Clinical practice guidelines also recommend anti coagulation in heart failure patients with a cardioembolic source (history of systemic or pulmonary embolism, or a mobile left ventricular thrombus). In the absence of above mentioned indications, anticoagulation is not recommended in patients with HFrEF.

Milrinone (Primacor®) is an inotropic/vasodilator agent with phosphodiesterase inhibitor activity (peak III cAMP-an isoenzyme of cAMP). It is also indicated for short-term I V treatment of HF. It does not cause thrombocytopenia (unlike amrinone), and it is not associated with tachycardia.

Decompensated HF patients admitted to hospital should receive VTE prophylaxis.

Rarely used: Prazosin and minoxidil are also afterload reducers but are associated with rapid development of tolerance and fluid retention. Nitroprusside is not used much now because of tolerance and toxicity problems.

Other Therapy

The 2013 ACC/AHA guideline update for the Management of Heart Failure recommends implantable cardioverter-defibrillator (lCD) for primary prevention of sudden cardiac death and to reduce total mortality in patients with HF (nonischemic dilated cardiomyopa thy or ischemic heart disease) who are at least 40 days post-MI and who have an EF :S 35% and NYHA III III symptoms on optimal medical therapy, or who are post-MI with EF :S 30% and NYHA I symptoms on optimal medical therapy. ICD candidates must also have an expected survival > 1 year. See Implantable Cardioverter-Defibrillators on page 5-44 for Class I indications for ICD therapy. Ventricular dyssynchrony is caused by electrical disturbances that cause the heart to pump blood in an inefficient way. It is suggested by severe HF (NYHA III! I V), severely decreased ejection fraction (LVEF :S 35%), and QRS exhibiting LBBB configuration with QRS duration 2: 120 ms. Cardiac resynchronization therapy (CRT) involves pacing the right and left ventricles and is recommended for patients with EF :S 35%, sinus rhythm, LBBB with a QRS duration of 2: 150 ms, and is NYHA II/III, or patients who are ambulatory with NYHA IV symptoms despite optimal medical therapy. (Per 2012 ACC/AHA update of device therapy guidelines.)

Emergency Treatment for Severe Heart Failure [Know:] With severe ventricular failure, patients may require short-term treatment with inotropes (dopamine, dobutamine, and milrinone). Dobutamine is another inotropic agent that can be used for severe ventricular failure. It does not have the vasoconstrictor activity of dopamine and actually has some vasodilatory effects.

•

Revascularization (CABG or PCI) is indicated for patients on optimal medical therapy with angina and suitable anatomy, especially left main stenosis (> 50%) or left main equivalent disease. For end-stage HF, cardiac transplant is the best option. There is a 65% 5-year survival and a 55% 10-year survival! Harmful for HFrEF patients: •

•

Definitely avoid or withdraw most antiarrhythmics, calcium blockers (except amlodipine), NSAIDs, and thiazolidinediones. Long-term use of positive inotropic drugs is potentially harmful, except as palliation for patients with end-stage disease (Stage D) who cannot be stabilized with optimal medical therapy.

HIGH-OUTPUT HF "High-output" ventricular failure is seen with peripheral shunting (large AV fistulas, severe hepatic hemangiomatosis, and Paget disease!) and low-systemic vascular resistance, as seen in gram-negative sepsis. You can also see it in patients with hyperthyroidism, beri beri, carcinoid, or anemia. Remember, though, these patients often have a normal cardiac output at the time of diagnosis-because of the worsening ventricular failure!

RIGHT VENTRICULAR FAILURE

Dopamine: •

Mechanical circulatory support (MCS) is beneficial in selected patients with Stage D HFrEF in whom defini tive management (cardiac transplantation) or cardiac recovery is anticipated or planned. Nondurable MCS (percutaneous and extracorporeal ventricular assist devices) are reasonable as a "bridge" to recovery/deci sion in carefully selected HFrEF patients who have acute, profound hemodynamic compromise. Durable MCS can be used to prolong survival for carefully selected HFrEF patients.

At < 2 J.lg/kg/min dopamine stimulates the dopaminergic receptors and causes mesenteric dilation. At 2-5 J.lg/kg/min, it has a predominantly beta agonist effect (positive inotropy) and increases renal perfusion. At> I 0 J.lg/kg/min, it mainly has an alpha-agonist effect and causes vasoconstriction. Generally never use> 10 J.lg/kg/min!

"The most common cause of right heart failure is left heart failure!" is what you heard on rounds. And, indeed, right ventricular failure (RVF) is mainly caused by pul monary hypertension (1° or 2°)-typically secondary to left ventricular failure (LVF). RVF is also seen with large RV infarctions and cor pulmonale. Remember: If the patient has signs of RVF (ND and liver congestion), but pressures are the same in all chambers in diastole, think external compression (constriction or effusion).

PERICARDIAL DISEASES

•

CRT is indicated for which HF

Know all drugs used for emergency treatment of

HF!

severe •

True or false?

MCS

is beneficial in selected

HFrEF

Suspect TB as the cause if the patient is at high risk, or if of treatment. Dressler

syndrome

and

postpericardiotomy

weeks after the precipitating event. Even if the history is and exclude them to make the diagnosis: MI, pulmonary

edema?

embolus, and endocarditis. Other causes include uremia and connective tissue disease.

What are some causes of non-constrictive

ECG

changes can you see?

LVF progresses, orthopnea

usually

Paroxysmal nocturnal dyspnea does not improve with sitting up, as orthopnea does.

PULMONARY EDEMA Immediate treatment for acute pulmonary edema: Patient should be sitting with legs dangling, if possible, to decrease venous return. Give I 00% 02, morphine (to decrease anxiety and decrease vasoconstriction). Give furosemide (causes venodilation even before the diuresis). IV nitroglycerin or nitroprusside can be used if systolic BP is > I 00. Strongly consider the use of dobutamine if systolic

•

BP<

Patients with pericarditis commonly present with very severe chest pain, sometimes pleuritic, which (classically)

RV function worsens due to the pulmonary hypertension.

•

Certain drugs, especially procainamide and

What is the treatment for acute pulmonary

Orthopnea: As

•

Open heart surgery (postpericardiotomy syndrome)

very suggestive, you must consider the following entities

worsens, but it may then actually improve temporarily as

•

MI (Dressler syndrome)

•

syndrome are autoimmune processes that occur several

With what diseases does high-output heart

pericarditis? What

•

Hypothyroidism

•

Both

failure occur?

•

Postradiation

•

the symptoms of pericarditis do not resolve after 2 weeks

in whom definitive

cardiac recovery is anticipated or planned.

•

hydralazine

IJg/kg/min)? At doses of 2-5 IJg/kg/min?

management (cardiac transplantation) or

•

Cancer

•

patients with stageD

•

Renal failure (uremic)

What does dopamine do at low doses

(< 2 •

patients?

•

90.

improves when leaning forward. The pain is retro-sternal and left precordial, and referred to the neck, arms, or left shoulder. Typically, the patient has some fever and tachy cardia. A pericardia! friction rub, which does not always occur and can be evanescent, is diagnostic for pericarditis. The ECG may show diffuse concave-up ST elevation (vs. localized, concave-down ST elevation in an acute MI) and, occasionally, depressed PR segments, especially in lead

II. ECG changes occur in 4 stages:

Stage I: diffuseST elevation segments with upward

•

concavity with PR depression Stage 2: normalization ofST segments after

•

several days Stage

•

3: inverted T waves

Stage 4: weeks or months after onset of acute

•

pericarditis, ECG returns to normal Pericarditis can cause transient increases in troponin (secondary to associated myocarditis). Treat pericarditis by stopping any possible causative drugs and giving

Aminophylline is rarely used to increase respiratory

NSAIDs. Do not treat idiopathic pericarditis with steroids

muscle function.

because there can be a relapse when they are stopped. Treatment with colchicine has been shown to reduce

PERICARDIAL DISEASES

recurrence.

NON-CONSTRICTIVE PERICARDITIS

CONSTRICTIVE PERICARDITIS

90% of non-constrictive pericarditis is idiopathic and

It occurs when resorption of pericardia! effusion is

probably viral in origin; often, there is a preceding URI or gastroenteritis. Causes of non-constrictive pericarditis:

(90%), probably viral

•

Idiopathic

•

Tuberculosis

•

Connective tissue diseases

Sepsis

•

followed by obliteration of the pericardia! cavity with scarring. Constrictive pericarditis must be differentiated from restrictive cardiomyopathy (page

5-48) because

the signs and symptoms can be similar. (Again:

Although

constrictive

pericarditis

often

quickly treated with good results, restrictive cardio myopathy is not reversible.)

5-55

5-56

PERICARDIAL DISEASES

Constrictive pericarditis may follow:

component ofHF, and BNP levels are markedly elevated (e.g., 8x max normal). With constrictive pericarditis,

Viral or idiopathic pericarditis

•

there is little or no actual HF, and BNP levels are

•

Traumatic hemopericardium

•

Tuberculosis

•

Cardiac surgery

•

Mediastinal irradiation

RECURRENT PERICARDITIS

•

Purulent infection

Recurrent pericarditis is a condition in which the only

•

typically just above normal.

disabling problem is the associated chest pain. It does

Histoplasmosis

not progress to constrictive pericarditis. It is only rarely

•

Rheumatoid arthritis

•

SLE

•

Neoplastic disease (especially breast cancer, lung

associated

arrhythmias.

Treat

with

NS AIDs,

does not have good results and is tried only after medical

cancer, and lymphoma) •

with

colchicine, and glucocorticoids. Pericardiectomy often treatment options have been exhausted.

Chronic renal failure with uremia treated by chronic dialysis

In constrictive pericarditis, ventricular filling is normal during early diastole but reduces abruptly when the

PERICARDIAL EFFUSION Pericardia! effusion is generally diagnosed with an

elastic limit of the pericardium is reached.

echocardiogram, but CT and MRI are the most accurate,

Constrictive pericarditis is characterized by rapid, early,

pockets of effusion. Surgical drainage is preferable in

diastolic filling of the LV, causing a loud presystolic knock just after S2. Pulsus paradoxus can occur but is usually mild.

Kussmaul sign: When, because the heart is encased

to differentiate constrictive vs. restrictive etiology. If

in a lack of the normal decrease in jugular venous

pericardiocentesis fluid is diagnostic in acute pericardia!

distention (ND) during inspiration. When severe,

effusion in an otherwise normal person, it is normally

ND can increase even during inspiration.

due to a neoplasm! (Read the previous sentence again

Large, right-sided x andy descents. This is seen as a

it's a little tricky.)

brisk collapse of the jugular veins during diastole.

the pericardium

can

cause

calcification

(-50%). You can see this best on the

lateral chest x-ray because it is typically found over the right ventricle, but you also can see it on the PA view and on CT. A lateral chest x-ray that shows calcification over the right ventricle is pathognomic for constrictive pericarditis. pericardium, but echo is also used. A pericardia! thick

5 mm is suggestive of, but not sufficient for,

diagnosis. The pericardium can be of normal thickness in -20-25% of cases of constrictive pericarditis. In

both

tamponade

Tamponade

[Know!]

critical

cardiovascular

compromise caused by a pericardia! effusion. There is obstruction to the inflow of blood to the ventricles. The most common causes are trauma, cancer, uremia, and acute pericarditis. When there is rupture of the free wall of the heart, as in trauma or post-MI, tamponade develops

quickly;

otherwise,

generally

develops

slowly.

CT and MRI are best for measuring thickness of ness of >

neoplastic, hypothyroid, and renal failure-related tam TB. Sometimes, you need an endomyocardial biopsy

is transferred to the venous inflow tract, resulting

Constrictive pericarditis

in diagnosis but is often used to treat viral, idiopathic, ponade. Pericardia! window biopsy can help diagnose

in a "shell," the negative pressure during inspiration

•

traumatic hemopericardium, post-surgical effusion, and when bacteria or TB is suspected as the cause of tampon ade. On the other hand, pericardiocentesis rarely helps

There are 2 clinical hallmarks of constrictive pericarditis: •

especially if the resultant tamponade is due to localized

and

constrictive

The

3 hallmarks of acute tamponade:

I) Hypotension and muffled heart sounds 2) Pulsus paradoxus (systolic BP drops> I 0 mmHg during inspiration)

pericarditis,

cardiac cath shows the same pressure during diastole in all 4 chambers. You can often make the differentia tion between tamponade and constrictive pericarditis at the bedside using these hallmark signs (see tamponade below). Constrictive pericarditis must be treated with an

3) Jugular venous distention with no collapse during diastole (i.e., an attenuatedy descent) Tamponade causes soft, distant heart sounds. Compare and know the difference between this and constrictive pericarditis (above).

open thoracotomy and pericardiectomy. Unfortunately, this resolves the problem only 50% of the time! Brain natriuretic peptide (BNP) plasma levels are being used to differentiate between constrictive pericarditis and restrictive cardiomyopathy. BNP increases with heart failure. With restrictive cardiomyopathy, there is a

CONGENITAL HEART DISEASE

Standard treatment had been open surgical closure, but now most secundum ASDs are closed percutaneously. If there is a> 2:1 left-to-right (pulmonary/systemic) shunt, a surgical closure is done, even if the patient is asymp •

•

What are the 2 clinical hallmarks of constrictive

tomatic. In this case, the ASD would eventually cause an

pericarditis?

increase in pulmonary vascular resistance and associated complications.

When is the measured diastolic pressure of all

Generally, severe, fixed pulmonary hypertension

4 chambers equal? •

How is BNP used to differentiate constrictive

the ASD.

pericarditis from restrictive cardiomyopathy? •

What treatments can be helpful in recurrent

Ostium Primum ASD

pericarditis? •

•

This form of ASD is seen most commonly in Down

Name the 3 hallmarks of cardiac tamponade.

syndrome. Patients with ostium primum atrial septal

What is the most common congenital

defect may have a loud pansystolic murmur 2° to mitral

abnormality found initially in adults? •

and/or tricuspid regurgitation. The regurgitation is due to the ostium being low on the septum, interfering with the

True or false? Ostium secundum ASD often has

function of the AV valves or left mitral valve. ECG has

right axis deviation and/or RBBB on EGG. •

left axis and RBBB.

When should surgery be performed for a secundum ASD?

•

Surgery for any type of ASD essentially cures the problem. Functional Class III/IV patients can revert to

What type of cyanosis would you expect to see

functional Class I with excellent survival! Eisenmenger

in someone with a PDA? •

considered a contraindication to surgical repair of

syndrome is a contraindication to ASD surgery.

What is the most common congenital defect in children?

Sinus Venosus ASD Sinus venosus ASD is

CONGENITAL HEART DISEASE

associated

with anomalous

pulmonary venous return because it occurs high on the septum. It is a cause of 10% of ASDs.

NOTE Most adult patients with congenital heart disease

are

asymptomatic! Know that the magnitude of any shunt does not depend on the total blood flow rate, but is commonlyly a constant ratio of pulmonic to systemic flow (Qp/Qs).

PDA Adult patients with patent ductus arteriosus (PDA) are usually asymptomatic; females > males. PDAs are typically discovered early by detection of the distinct murmur. Endarteritis can occur in PDA.

ASD

PDA causes a continuous, "machinery" murmur at

Ostium Secundum ASD

the LUSB. As pulmonary pressures rise, the murmur

Secundum atrial septal defect comprises 70% of all atrial

becomes

septal defects (ASD). It is the most common form of

(e.g., clubbed toes, normal fingers) with pulmonary

congenital heart disease found initially in adults (F> M),

hypertension is possible.

excluding a bicuspid aortic valve. With a large secun dum ASD, there is a systolic ejection murmur at the left sternal border (2° to increased flow across the pulmonic valve), occasionally a diastolic murmur (from increased

less

continuous.

Differential

cyanosis

Chest x-ray shows calcification of the ductus arteriosus in adults. If the patient develops pulmonary hypertension, consider

flow across the tricuspid valve), and a fixed split S2. The

Eisenmenger syndrome (see page

left-to-right shunt causes diastolic overloading of the

Surgical or percutaneous closure in symptomatic patients

right ventricle and increased pulmonary blood flow with

has

inspiration and expiration.

from surgery.

ECG

shows

right

axis

deviation

and/or

enlarged RV with shunt vasculature. Notice all of the right-sided stuff with ASD-makes sense because ASD causes a volume load on the right side of the heart.

excellent results. Elderly patients

also

benefit

right

bundle-branch block (RBBB). Chest x-ray shows an

Patients can develop 2° atrial fibrillation.

5-58).

PULMONARY STENOSIS Balloon valvuloplasty is the procedure of choice for treating pulmonary stenosis. It has favorable long-term clinical and hemodynamic results.

5-57

5-58

PULMONARY HEART DISEASE

Etiologies of sudden death in exercising young people:

VSD Ventricular septal defects (VSDs) are the most common

•

congenital defect in children. They are uncommon in

•

adults because most have either closed spontaneously

•

or have been surgically closed in childhood. 80% of

•

small VSDs close spontaneously in the first I 0 years

•

of life. Large VSDs usually require surgery (although even I 0% of these eventually close spontaneously).

•

Myocarditis (5.9%) Arrhythmogenic RV cardiomyopathy (4.3%) Ion channelopathies including long QT syndrome

OTHER Marfan syndrome causes decreased strength of the aorta

COARCTATION OF THE AORTA Know that a bicuspid aortic valve occurs in

Coronary anomalies (17%) Possible HCM (8.2%)

([LQTS]; 3.6%)

A loud holosystolic murmur is heard at the left lower sternal border.

HCM (36%)

�

50% of

patients with coarctation of the aorta (COA)! Other associated anomalies include mitral valve problems, left ventricular myocardium problems, and membranes in the left atrium. Notice that all of the heart problems associated with coarctation of the aorta are left-sided!

(with aortic regurgitation and dissection) and mitral regurgitation. Rubella causes congenital pulmonic steno sis, PDA, and multiple pulmonary artery stenoses. Cystic fibrosis can eventually cause pulmonary hypertension.

PULMONARY HEART DISEASE

The classic physical findings are either a delayed fem oral/brachial pulse (feeling the brachial and femoral pulses, there is a distinct delay in femoral pulse) or an absent femoral pulse. Patients can have upper-body hypertension and can get hypertensive aneurysmal dilatation and rupture of the circle of Willis. Look for rib notching on chest x-ray due to the collateral

COPD AND SLEEP APNEA The most common causes of pulmonary heart disease are COPD and sleep apnea syndrome. These two are covered extensively in Pulmonary Medicine, Book 2, so we will cover the other causes here.

vessels getting very large and eroding the ribs. Turner syndrome is associated with coarctation of the aorta and a bicuspid aortic valve.

EISENMENGER SYNDROME Eisenmenger

syndrome

occurs in

patients

with

large, intracardiac shunt when the pulmonary vascular

ANOMALOUS CORONARY ARTERY

resistance

Pre-mortem detection is extremely difficult and requires a high index of suspicion. This can present as exertional chest pain or exertional syncope in a young, otherwise healthy individual. Syncope after exercise can occur in "normal" people, but syncope during exercise is never normal. With anomalous coronary artery, there is an abnormal course of I of the 2 coronary arteries between the

becomes

greater

than

systemic vascular

resistance-so, the shunt becomes right-to-left instead of the more normal left-to-right. It is a result of severe pulmonary hypertension, which can develop early (or late) in patients with large, cardiac, left-to-right shunts of virtually any type: VSDs, PDAs, and ASDs. Cyanosis is common. Heart-lung transplant is the only effective treatment for Eisenmenger syndrome.

2 great vessels, the pulmonary artery and aorta. At rest,

CHRONIC THROMBOEMBOLIC

there is plenty of room for the vessel to pass without

OBSTRUCTION

compromise; however, in extreme exercise, the cardiac output can increase 4-8-fold. This expands the elastic pulmonary artery and aorta, resulting in compression of the coronary artery as it courses between the great vessels. This compression creates coronary ischemia and arrhythmias.

Chronic thromboembolic obstruction mainly occurs as a result of impaired fibrinolytic resolution of acute thromboembolism, leading to organization, incomplete recanalization, and chronic obstruction of the pulmonary vascular bed. Most patients treated for acute pulmonary thromboembolism do not develop chronic pulmonary hypertension.

Chronic

thromboembolic

obstruction

SUDDEN DEATH IN EXERCISING

is also the result of other causes of secondary pulmo

YOUNG PEOPLE

nary hypertension such as large left-to-right shunts and

The most common cause of death in exerctsmg young people is HCM (36%). Next most common are coronary anomalies (17%)-although this is a more likely cause in the 30-40-year-old group. Also consider primary pulmonary hypertension as the cause in young women.

chronic LVF. Progression of this disease probably results from the pulmonary arteriolar changes (instead of more PEs); these are similar to the changes that develop with large septal defects. The resultant increased pulmonary vascular resistance causes RVF. Surgical removal of the

thromboembolic

material

results

significant

PREGNANCY AND THE HEART

Warfarin is contraindicated in pregnancy due to its teratogenic effects. It is absolutely contraindicated in the I st trimester; although, to be safe, most physicians do not give it at all during pregnancy. Heparin, LMWH, •

What are the 2 most common causes of sudden

digoxin,

death in an exercising young person? What third

blockers, and DC cardioversion are not contraindicated.

What is the only effective treatment for

A maternal a

What are the 2 cardiac-related absolute

rubella

common cause

HCM

True or false? Warfarin is not contraindicated

infection

during

supravalvular

pregnancy

aortic

stenosis,

among

asymptomatic

women

not

contraindication for pregnancy. In women with HCM

in pregnancy. •

channel

pulmonic stenosis, and other congenital cardiac defects.

contraindications to pregnancy? •

calcium

increased morbidity and mortality in mother and child.

Eisenmenger syndrome? •

propranolol,

Although heparin is not contraindicated, it does cause

cause do you consider in young women? •

quinidine,

who are asymptomatic or whose symptoms are controlled

Know how to very quickly determine the axis

with

of an ECG. Brand Figure 5-7 into your brain!

beta-blockers,

the

beta-blockers

should

continued during pregnancy with increased surveillance for fetal bradycardia, cretinism, or intrauterine growth

improvement. Vena cava filters may be used in patients

retardation.

with deep vein thrombosis (DVT). Anticoagulate.

provocable LVOT obstruction

PULMONARY ARTERIAL HYPERTENSION

alone, pregnancy is associated with increased risk; refer

women

with HCM and

resting

(2: 50 mmHg) and/or

cardiac symptoms not controlled by medical therapy

Note that the terms for this disease are changing. Previously

was

called

idiopathic

pulmonary

hypertension (IPH), and before that, primary pulmonary hypertension. The

World

Health O rganization

has

reorganized causes of pulmonary hypertension into

5 groups of which !PH is now part of Group

Pulmonary arterial hypertension (PAH). PAH

includes

the

"sporadic

idiopathic

pulmonary

hypertension" that commonly occurs in young women, is refractory, and results in death within

5-10 years.

Treatment: Calcium channel blockers (in patients who are "reactive" to vasodilator testing) and sildenafil (Viagra®, Revatio®) are helpful. Endothelin antagonists and prostacyclins can

also

use.

Heart-lung

transplant is occasionally used. It is important to differentiate between 1 o and 2° because surgery may help 2° PAR.

A heart catheterization

rules out secondary causes such as right-to-left shunt and chronic LVF. A perfusion lung scan rules out PE. Pulmonary capillary wedge pressure (PCWP) is, of course, increased only in the pulmonary hypertension caused by, or concurrent with, LVF.

PREGNANCY AND THE HEART Pregnancy:

Absolute contraindications to pregnancy

include PAH and Eisenmenger syndrome (particularly deadly if cyanosis is present);

both are discussed

above. In secundum ASD, aortic stenosis, and dilated cardiomyopathy, the patient must be closely watched. In aortic stenosis and dilated cardiomyopathy, patients are typically kept at bed rest. Secundum ASD patients are normally not at risk for cardiac decompensation, unless they develop atrial fibrillation.

these patients to a high-risk obstetrician. Most pregnant women experience some pedal edema. F low murmurs and S3 gallops are also common, and the jugular venous pressure increases. Remember to rule out both mitral stenosis and secundum ASD in the pregnant patient presenting with new-onset atrial fibrillation and pulmonary edema.

5-59

5-60

THE ELECTROCARDIOGRAM

THE 12-LEAD ECG

THE ELECTROCARDIOGRAM THE 12-LEAD ECG F irst, we will briefly go over the basics of ECGs. Refer to Figure 5-7 as we go through this. A lead tracing is positive if the wave of depolarization spreads toward the positive pole of that lead, and it is

I &aVL: Lateral Leads

negative if it spreads away from the positive pole. The tracing is zero if the wave spreads at a 90° angle to it. For instance, if

is zero, look for the maximum projection

to be at aVL (either + or -).

THE FRONTAL LEADS

With the 12-lead ECG, the wave of depolarization is recorded on both the frontal and horizontal planes and gives a 3-dimensional representation of the heart. The projection of the electrical activity of the heart onto the frontal plane is recorded by the frontal leads

III,

I, II,

II, III, aVF: Inferior Leads

aVR, aVL , and aVF. On the horizontal plane, it is

recorded via electrodes placed in the V l -6 position.

Figure 5-7: Axis Determination Diagram

Occasionally, a V3R and V4R (placed same as V3 and V4, except on the right side of the chest) are used to better monitor the right side of the heart (e.g., right sided ischemia). Depolarization moving toward the lead causes a positive deflection (P wave and QRS), as does repolarization moving away from the lead (T wave). The

frontal

leads

give

information. For example,

posterior hemiblock(LPHB), RVH, and acute or chronic RV overload syndromes such as pulmonary hypertension! embolism,

and

pulmonic

stenosis.

adult

incidentally found to have RAD, do further workup.

inferior-superior-left-right

II, III,

and aVF cover the

RATES AND INTERVALS

inferior area. ST variations/Q waves occur in these leads with inferior ischemia and infarction.

The ECG is recorded on paper with a 1 mm2 graph, with

anterior-posterior-lateral

a thicker line every 5 mm. Because the paper moves

information. Think of VI as looking at the right side of

at 25 mrn!s, each thicker line is 115 of a second-or

the heart while V6 looks at the left side. The QRS in VI

0.2 sec(200 ms), and each mm represents 0.04 sec(40 ms).

is positive when the right ventricle(RV) is depolarizing

The interval covering 5 thicker lines (or "big squares")

The

horizontal

leads

relay

(and negative when the LV is depolarizing), whereas the QRS in V6 is positive when the LV is depolarizing.

is 1 second. There are a couple of quick ways to determine the heart rate. I'll discuss the RR interval, but any prominent

wave of the standard QRS may be used to determine the

AXIS DEVIATIONS

interval. Using a calculator, a quick and accurate method

The normal mean QRS axis is between -30° and +100°.

So, if the beat interval is 28 mm, the rate is 1,500/28 =

+100° is right axis deviation (RAD), whereas< -30°

is left axis deviation (LAD). A quick, fairly accurate method to determine this is to just look at

and aVF.

If both are prominent, you can quickly tell in which quadrant the mean vector lies. Visualize the following: Both

•

I(+) and aVF (-)=check for LAD

normal

•

Both(-)

•

I(-) and aVF (+)=check for RAD

54 bpm. A less accurate, but easier, method is to divide 300 by the number of "big squares" in the RR inter val. If the beat interval is 28 mm, this is not quite 6 big squares. You divide 300 by 6 and get 50, but you know the heart rate is actually a little faster because the inter val is not quite 6 big squares. A derivative of this is the

•

(+)

for determining heart rate is 1,500/RR interval in mm.

method taught in Dubin's book,

of EKG s,

extreme right or left axis

Rapid Interpretation

in which you memorize 2 sets of triplicates:

300-150-100 and 75-60-50. These match to the heart rates corresponding to RR intervals of 1, 2, 3, 4, 5, and

Left axis deviation(LAD) is usually due to left anterior

6 big squares.

hemiblock and, therefore, is a marker for CAD-as are

Normal rate is 60-100 bpm. Sinus tachycardia is defined

all fascicular blocks. Right axis deviation

as a sinus rhythm of

(RAD)

is often a normal finding

in children and young adults. Other causes include left

100 bpm; sinus bradycardia is

< 60 bpm. So, an RR interval < 3 big squares indicates tachycardia;

5 big squares indicates bradycardia.

Infringements to copyright@medstudy.com

THE ELECTROCARDIOGRAM

INTERVALS

•

Hypothermia Type la and III antiarrhythmics (Ia = quinidine, procainamide; III= amiodarone, sotalol)

More recently discovered causes of prolonged QTc are:

•

What are the causes of left axis deviation?

•

What are the causes of right axis deviation?

•

Does RAD always warrant additional workup

•

terfenadine (since pulled from the market}-their QT prolongation tendency can be increased by erythro

in an adult? •

mycins, some "azoles" such as ketoconazole, and

Name the causes of prolonged

QT intervals.

hepatic dysfunction.

Yes, all of them that are listed in the text! •

Non-sedating antihistamines such as astemizole and

•

amiodarone, sotalol.

What are the P wave findings for RAH? For LAH?

•

Liquid protein diet.

Short QTc can be caused by hypercalcemia and digitalis.

INTERVALS PRINT ERVAL

WAVEFORM S AND SEGMENTS

The PR interval indicates the time between atrial and ventricular depolarization. Normal duration is 3- 5 small squares (120-200

ms). Longer than 200

square) is the definition of Shorter than 120

Drugs such as methadone, phenothiazines,

ms (1 big

I 0 AV block.

PWAVE The P wave results from the depolarization of the atrium. The normal P wave is

ms (3 small squares) may indicate

WPW (delta wave), junctional rhythm (with retrograde P wave-see next), or left atrial overload (widened P

mm in height and

120 ms

(3 small squares) in duration, and the normal axis is-50 to +60 degrees. (Where else have you seen 120 ms? The normal PR interval is 120-200 ms.) See Figure 5 -8.

wave-see next).

Most information from the P wave can be derived from

QRS DURATION

from the SA node high in the right atrium and through

II, a VR, and Vl. As the wave of depolarization spreads the right and then left atrial myocardium, the mean

QRS duration is normally

100

ms (i.e., 1 /2 a big

square). QRS > 120 ms may be caused by bundle-branch block, ventricular beat/rhythm/ventricular pacemaker, drugs such as tricyclics, and WPW. I00-120 ms is often due to an incomplete 888.

vector is downward and to the patient's left-so the normal P wave is positive in

II and negative in aYR.

A retrograde P wave is negative in II and positive in a VR-indicating an ectopic focus originating in the inferior part of the atrium or at the AV junction, result ing in a wave of depolarization traveling toward a VR

QT INTERVAL The

interval

(picture this!). A retrograde P wave from the AV junction corrected

for

rate

normally

340-4 70 ms depending on gender and age. QTc

(RR)05;

QTI

often causes a tracing with a short PR interval. Because atrial depolarization traverses from the patient's

that is, the QT interval (in ms or sec) divided

right to left, the left/initial side of the P wave represents

by a conversion factor that, although dimensionless, is

the right atrium, while the right/terminal side of the

derived from the square root of the beat interval in sec

P wave represents the left atrium (mid-P wave is both).

onds. Again: The

RR interval in this calculation must be

in seconds. (Consider the difference in dividing by the square root of0 .7 vs. the square root of700 !) When scan ning ECGs, a rule of thumb is: The QT interval normally is�40% of the RR interval-- do the calculation for QTc if it appears shorter or longer.

E1G

With prolonged QT"' there is a tendency to develop

torsades de pointes.

Prolonged QTc has many causes: •

•

Normal

LAH

RAH

RA LA

tfT:

1\r-

II'"""

----'

Tricyclic overdose Hypocalcemia Hypomagnesemia Hypokalemia

\___.f-

--'

vI\

If1'--

Starvation CNS insult

F i gure 5-8: P Wave in Atnal Enlargement

5-61

5-62

WAVEFORMS AND SEGMENTS

THE ELECTROCARDIOGRAM

The normal P wave is positive in lead II and positive or

•

biphasic in V1; when biphasic, the P wave is positive on

•

Metabolic abnormality Intracerebral hemorrhage

the left side and a little negative on the right side. This is because the wave of depolarization through the atrium is toward V1 in the right atrium (left side of P wave) and somewhat away from V1 in the left atrium (right side of right

atrial

preponderance,

(enlargement,

hypertrophy, overload), the right atrial (initial) portion of the P wave is widened, and therefore overlaps onto the left atrial portion of the P wave. The P wave width stays normal

The U wave occurs just after the T wave. It is commonly small and is best seen in V2-3. If seen, it is usually a

P wave). With

UWAVE

(< I20 ms), but look for an increased P wave

< 1 mm, rounded deflection in the same direction as the T wave. If the U wave is prominent, there is an increased

tendency for torsades de pointes. Prominent U waves are present with hypokalemia, bradycardia, digitalis, and amiodarone.

amplitude in II (also III and aVF, but just look at II) and

Negative U waves are considered significant-even

in VI (the positive portion). Actually, the P wave being

if the rest of the ECG is normal! Causes are ischemia,

"peaked" in II is more important than it being tall. Decreased

wave

amplitude

seen

severe

hyperkalemia.

HTN, AV valve disease, and RVH. Negative U waves occur in up to 60% of patients with an anterior MI, up to 30% of patients with an inferior MI, and up to 30% of angina patients.

With left atrial overload, the right side of the P wave is enlarged, resulting in a wide P wave with a shortened or absent PR interval (i.e.,

< 120 ms). Other typical

findings are a widened notched P wave in II and an

ST SEGMENT There are 3 main causes of ST-segment elevation: acute

enlargement of the negative portion of the P wave in V1.

MI, Prinzmetal angina, and pericarditis. It may also

The most sensitive ECG finding for left atrial enlarge

be present with early repolarization variant, intracere

ment is a negative P wave in VI, with a duration of

bral hemorrhage, hypertrophic cardiomyopathy, LVH,

> 40 ms (1 small square). On the other hand, the most specific ECG finding is a notched P wave (usually in II) with an interpeak distance of> 40 ms. COPD: B ecause of the hyperexpanded lungs, the heart

LBBB , cocaine abuse, myocarditis, and hypothermia. ST-segment depression occurs with: •

or flat), such as seen in classic angina.

assumes a more vertical position, and there is resultant RAD of the P wave. A +90° P wave axis is highly sug

•

gestive of COPD. The pulmonary hypertension may

•

sion in inferior leads with some anterior/septal Mis. •

TWAVE The T wave is ordinarily in the same direction as the in the opposite direction of depolarization.

•

Hyperacute MI Intracerebral hemorrhage In septal leads (V1-2) in evolving post-MI

Focal-flipped T waves may accompany: •

•

RVH that may cause RAD and ST-segment depression preceding a flipped T wave in VI.

•

Digitalis toxicity. Hypokalemia.

QRS COMPLEX In QRS complex,

depolarization

the

ventricles

occurs simultaneously after the depolarization of the interventricular septum. The normal mean vector of

Ischemia

depolarization of the interventricular septum points

V1-2 with RBBB , RVH, and RV HTN

from the patient's left to the right across the septum. You

VI-2 with LVH L ateral leads (I, aVL , V6) with LBBB The precordial leads with LVH with "strain"

Diffuse flipped T waves may accompany: •

Isolated RV infarction, when there is ST elevation in Vl and ST depression in V2.

•

Peaked T waves are sometimes associated with the

•

LVH with LV strain (ST depression with flipped T waves in precordial leads).

QRS, indicating that repolarization is actually occurring

Hyperkalemia

R eciprocal depression in V1-2 with some inferior extension. There may also be reciprocal ST depres

P wave changes (see previous discussion).

•

ST depression in V1-2 with an acute posterior MI. wall Mls-especially those with lateral or posterior

result in right atrial preponderance with associated

following:

Subendocardial ischemia (especially if downsloping

Pericarditis Diffuse ischemia ; post-resuscitation

see this as a small initial deflection, which is positive in V1 (R wave) and negative in V6 (Q wave) (Figure 5-9). The left ventricle is normally much more massive than the right ventricle; therefore, the mean QRS vector (reflecting depolarization of the ventricles) is strongly to the patient's left. You see a large negative deflection in VI and positive deflection in V6. On the frontal plane,

THE ELECTROCARDIOGRAM

VENTRICULAR HYPERTROPHY

E& •

•

When are peaked T waves seen?

When are focal-flipped T waves seen? U waves indicate a predisposition to what serious condition?

•

~ Sand Q variable

L+ G R �V d e R

What are the common causes of U waves? Name the 3 main causes of ST-segment

What are the causes of ST-segment

depression? •

RVH

~ 1-s

What is the significance of a negative U wave?

elevation. •

LVH

Normal

Figure 5-9: Ventricular Hypertrophy

What are the ECG criteria for LVH? RVH? In LBBB, the left side of the septum depends on

to check the PR interval-you might be looking at a

what to depolarize?

delta wave in WPW! as mentioned above, the mean vector is between -30

Although the specificity of the various ECG criteria

and +I 00 degrees.

for LVH is quite high at

95%, the sensitivity is low

t i n U

and varies from 25% for the above criteria to 50% for

The normal duration of the QRS is< 100 ms.

a complicated point system. Note that if the prevalence

QRS changes seen with ventricular hypertrophy and conduction disturbances are discussed next.

of LVH in a population is 5%, there are many more false negatives and many more false positives than true positives, making this fairly useless as a screening test. (Go and work this out using the Bayesian 4-square!

VENTRICULAR HYPERTROPHY LVH

Population I 0,000; sensitivity = 25%; specificity

LVH (left ventricular hypertrophy) causes a prolongation

9 ri 9

of activation of the myocardium. It is thought that rela tive coronary insufficiency (increased muscle mass >

increase in size of the capillary bed) may be a factor

in this prolonged activation. Another factor may be

the overgrowth of the muscle mass relative to the Purkinje system.

h ta

This prolongation of activation, in addition to moving

95%; find all the other numbers. Answer: TP

475, FN = 375, TN= 9,025; PPV

NPV

125, FP

2 1% [not good!];

96%. Statistics are covered in General Internal

Medicine, Book 5.)

When there is left axis deviation, the ECG criteria for LVH change! Use: SIII> 15 mm (Rosenbaum). A left ventricular "strain" pattern may be present with LVH. LV strain is precordial ST-segment depression and

flipped T waves seen in a patient with ECG criteria for LVH.

the mean QRS axis more posterior, superior, and to the left, also results in a reversal of repolarization, which now proceeds from the endocardium to epicardium,

RVH

and is reflected by a flipped T wave in the septal leads

Because RVH (right ventricular hypertrophy) is such an

(VI-2).

abnormal condition, with the mass of the right ventricle

LVH causes an exaggeration of the negative deflection in VI and the positive deflection in V6. There are sev eral accepted ECG criteria for LVH, including: SV 1 +

increasing to the point of shifting the mean QRS vector to a right axis, the specificity for RVH is very high when ECG criteria are met-although, as with LVH criteria,

(RV5 or RV6) > 35 mm or (RV5 or RV6)> 25-35 mm.

the sensitivity is low.

This is read "the S in Vl +the R in V5 is> 35 mm," etc.

ECG criteria for RVH are right axis deviation and,

(Figure 5-9).

again, because of repolarization changes, ST-segment

The diagnosis of LVH is strengthened by an intrinsicoid

depression and a flipped T wave in VI, sometimes in

deflection of > 50 ms ( 1.25 small squares). This is the

V2. The ST-segment depression and flipped T wave

time from the beginning of the QRS complex to the

generally indicate RV stress/hypertension (Fig ure 5-9).

peak of the R wave. For greater ease of use, intrinsicoid

Pulmonary embolism

deflection is often called the "R peak time." Note: When

severe pulmonary embolism (acute cor pulmonale),

you notice an obvious intrinsicoid deflection, make sure

(PE):

Note

that with acute,

ECG changes are reflective of acute RV strain with RV and RA dilation +/- ischemia. There is often a R BBB,

5-63

5-64

CONDUCTION DISTURBANCES

THE ELECTROCARDIOGRAM

sometimes RAD, and usually clockwise rotation. Because these are all nonspecific findings, and because of the changing nature of this event, the most important factors that increase sensitivity of the ECG in the setting of possible PE is a prior ECG tracing for comparison and serial tracings after admission. S l Q3T3 pattern (S wave in lead I, Q wave in lead III, and an inverted T wave in lead III) is an indication of RV strain and is a specific, but not sensitive, indication for acute PE.

CONDUCTION DISTURBANCES AVBLOCKS

Atrioventricular (AV) blocks are due to conduction disturbances at the AV node. Know the 3 degrees and their patterns. 151 >

200 ms ( l big square).

251 •

•

degree AV block prolongs the PR interval by degree AV block results in 2 main patterns:

Mobitz I, Wenckebach phenomenon: progressive pro longation of the PR interval until there is a dropped QRS (ventricular beat). Mobitz 2: Normal PR intervals, but periodically there is a dropped QRS. 2: l AV block is 2 P waves for each QRS, 3: l is# of P waves for each QRS, etc. Mobitz 2 almost always has a wide QRS complex (if narrow, typically Mobitz 1).

3rd

h a

The T wave vector and sometimes the ST segment are opposite in direction to the mean QRS vector in LBBB. Therefore, as illustrated in Figure 5-l 0, you see nega tive T waves following the positive RR' in I, a VL, and V6-and positive T waves following the negative QRS in Vl-3.

G R

Important note: In LBBB, the left side of the septum depends on myocardial conduction to depolarize; hence, conduction is slow over the left side and depolariza tion progresses from right to left, causing an rS or QS in V l . This right-to-left depolarization of the septum overcomes the expression of any septal Q waves with an MI-including the inferior leads. So, just as new septal Q waves do not appear in a patient with LBBB and an acute MI, MI-related septal Q waves disappear if LBBB develops because of the MI. Therefore, LBBB makes it impossible to use the ECG as an evaluation tool in a patient you suspect of having an MI.

V d ti e

Criteria for LBBB: •

•

QRS 120--180 ms (3-4.5 small squares). The left ventricle is depolarized, later resulting in an RR' (slurred or notched) in V6 and an SS' (QS) in VI. The T wave is often opposite the mean QRS vector in anteroseptal and lateral leads. =

Incomplete LBBB fulfills the above criteria, except QRS < 120 ms. RBBB

Right bundle-branch block (RBBB): The direction of septal depolarization is normal-left to right, but

BUNDLE-BRANCH BLOCK Overview

Left bundle-branch block (LBBB): The QRS is prolonged with a duration of 120--180 ms (3-4.5 small squares). Because the left ventricle depolarization is now transmyocardial, it is depolarized over a longer period, resulting in an RR' (notched or slurred) in the lateral leads (I, aVL, and V6), and there is a corresponding SS' (also called QS) in VI. 112 of patients have a normal axis, l/2 have LAD (-30° to -90°).

n U -

degree AV block: No depolarizations are conducted through the AV node. The P wave and QRS have inde pendent regular rhythms (AV dissociation). If the QRS complex has a normal width (< I00 ms), there is a junc tional ectopic pacemaker. Junctional pacing rate is 40--60 bpm, whereas ventricular pacing is 20-40 bpm. Note: The AV node has no pacemaker activity. Junctional pacing originates from the myocardial tissue at the AV junction. (It may be near the AV node, but it is not a part of the AV node!)

9 9

LBBB

Just a little after the AV node, the fast conduction pathway, known as the bundle of His, splits in two. These 2 fast conduction pathways travel down the interven tricular septum, and one then goes to the right ventricle, while the other one-functionally if not anatomically splits again and proceeds to the anterior and posterior sections of the left ventricle. If conduction in one of these pathways is blocked, the depolarization downstream to that pathway is delayed because the myocardial tissue in that area can then be depolarized only via the depo larization wave from much more slowly conducting adjacent myocardial tissue. Refer to Figure 5-10.

E� VI

Normal

f. t \"(: j:_ ~ (

LBBB

RBBB

)

F i gure 5-10: Bundle-Branch Block

THE ELECTROCARDIOGRAM

ARRHYTHMIAS

5-65

LPFB Left posterior fascicular block (LPFB) or left posterior hemiblock (LPHB): This problem is rare, and the ECG •

•

pattern is rather nonspecific because you can also see

What do you see on an ECG in LBBB? RBBB?

it in patients with RVH, lateral infarction, and emphy

What is so serious about a recent Ml and the

sema. You can be sure that it is a LPFB only if it is a

development of a bifascicular block?

recent change-all else being the same. The septal depolarization is left to right but directed superiorly,

What is the difference between an ectopic beat

causing a small Q wave in the inferior leads. Because

and an escape beat?

final depolarization in the heart is in the inferior and

the right ventricle is depolarized over a longer period, resulting in an RR' or RSR' ("rabbit ears") in V1 and an

posterior walls with the vector pointing inferior and to the right, there are large R waves in the inferior leads (II, III, aVF) and large abnormal S waves in the lateral limb

S wave in V6. Visualize how the RSR' in V l is formed:

leads

The initial R wave is due to normal left-to-right septal

+80° to + 140°. The T wave is normal.

Criteria for LPFB:

til

depolarization, the S is depolarization of the left ventri cle, and the final R' is due to the delayed depolarization of the right ventricle. In V6, the S wave is due to delayed depolarization of the right ventricle.

•

QRS > 120 ms (3 small squares).

•

Depolarization of the right ventricle is delayed, result a slurred S wave in V5-6.

Incomplete RBBB fulfills the above criteria, except QRS 120 ms.

LAFB

9 ri 9

Bifascicular block has 3 presentations: I) Complete LBBB

2) RBBB + LAFB

Flipped T waves in VI, sometimes V2.

Left anterior fascicular block (LAFB) or left anterior hemiblock (LAHB). QRS duration is 100-120 ms.

Septal activation is in a left-to-right (normal) and infe

rior direction. This inferior septal depolarization is

sometimes reflected in a Q wave in the lateral leads (I and aVL). Because the last part of the heart to depolar

h ta

Rightward axis ( +80° to +140°)

Bifascicular Block

ing in an RSR' ("rabbit ears") or RR' in V l and often

aVL

•

Criteria for RBBB:

G R

Small Q and large R (qR) waves in II, III, and aVF Small R wave in I, followed by a large S wave in I,

V d ti e n U •

The T wave is usually negative in VI, sometimes in V2.

•

(I, aVL). This also results in a mean QRS axis of

ize is the left posterobasal to anterolateral wall, the mean frontal QRS vector has a left-facing axis (-45° to 0°). This also causes lead I to record a large R wave and the

3) RBBB + LPFB

The last is the least common. Anterior MI and calcific

aortic stenosis are associated with bifascicular block.

Remember that acute MI + a new bifascicular block indicate a high risk for progression to complete heart block.

WIDEQRS Wide-complex QRS may be caused by BBB, ventricular origin of the complex, and/or aberrant conduction. More on this is discussed next and under the previous Arrhythmia topic on page 5-38.

inferior leads to record a large S wave. Left axis devia tion (LAD) more negative than -45° with a normal QRS

ARRHYTHMIAS

duration is nearly always due to LAFB. Actually, LAFB is the component that causes the LAD in 1/2 of patients with LBBB. Criteria for LAFB: •

Left axis deviation (LAD) -45° to -90°, with a large S wave in the inferior leads (II, III, and aVF) and a dominant R wave in I

•

Absence of other causes of LAD (incomplete or complete LBBB)

•

Poor R wave progression across the precordium

ECTOPIC

vs.

PACEMAKER

An ectopic beat occurs from an ectopic (abnormal) focus earlier than the expected next beat. It may originate in the atria, AV junction, or the ventricle. Throughout the heart are foci of cells with pacemaker capability, which can take over if there is a delay in depolarization, such as when the SA node ceases to function normally or there is a severe conduction disturbance. Atrial, non-SA node pacemaker activity has an inherent rate of 60-80 bpm. AV junction (not AV node!) pacemaker rate is 40-60 bpm. Ventricular pacemaker rate is 20-40 bpm (idioventricular rhythm).

MedStudy

(") G)

5-66

THE ELECTROCARDIOGRAM

MYOCARDIAL INFARCTION

Note that ectopic beats are different from escape/ pacemaker beats. Ectopic beats are early. Escape beats are at the rate of inherent pacemaker activity.

VENTRICULAR ECTOPIC BEATS AND HEART BLOCK Premature ventricular contraction (PVC):

ATRIAL ARRHYTHMIAS

•

TheQRS complex occurs earlier than expected (premature), is wider than normal, and has a higher

Atrial fibrillation:

amplitude than normal.

•

No P waves: "irregularly irregular" rhythm

•

Clinically: varying pulse pressure and no

•

waves

P wave is obscured in theQRS complex. T wave is inverted.

•

Atrial fibrillation is the result of multiple ectopic foci

The next RR interval is longer than normal. This is

•

called a full compensatory pause. The SA node is not

firing continuously or disorganized atrial activity. It is

reset by the ventricular depolarization-hence, the

thought to be due to a micro-reentry mechanism. No

P waves march out normally.

P waves are seen, although there is loud, chaotic atrial "noise" throughout the tracing. Atrial flutter ( Type •

1):

kick in.

High atrial rate: characteristic rate� 300 bpm

Complete (3rd degree) heart block has an atrial beat

(range 240-340), typically with a 2:1 AV block •

Sawtooth formation

•

Whole number ratio of flutter waves toQRS

marching independently of a junctional or ventricular

V d ti e

escape beat. Remember junctional = narrow, 40--60 bpm. Ventricular = wide, 20-40 bpm. Medication and certain

complexes

illnesses can affect these rates.

Atrial flutter is due to a wave of depolarization repeatedly going around and around the atrium-usually with an anatomic obstacle, such as an AV valve, in the pathway. This results in the "sawtooth"-appearing P wave with

Study tip: Now is a good time to review ventricular tachycardias vs. aberrant conduction. See the discussion on page 5-43.

n U -

an atrial rate of � 300 bpm (but it varies between 240

and 340 bpm). There is commonly a 2:1 or 3:1 AV block with a resulting ventricular rate of 150 or 1 00, respectively.

MYOCARDIAL INFARCTION

COMMON FINDINGS

There is also a Type II atrial flutter with a much higher atrial rate: 340-440 bpm. Wandering

G R

A ventricular escape beat may occur if the sinus pause is long enough, and no atrial or junctional pacemakers

pacemaker

9 9

exactly

what

the

name

implies. The pacing impulse migrates from one atrial pacemaker focus to another. It is a benign condition

r i h

seen mostly in young people-especially athletes. The varying focus is reflected by varying shapes of the P wave.

Multifocal atrial tachycardia

[Know this section!] Common findings in myocar

dial infarction: Within the first minute or so of acute ischemia, the T waves flip. After 1-2 minutes, they

become positive and peaked (hyperacute). Then injury to the cells occurs, causing the S T segment to elevate.

Q waves are associated with cell death. These associa tions of ECG changes with the actual pathophysiologic processes are somewhat artificial, but clinically useful.

(MAT) is similar to

wandering pacemaker, except that MAT occurs at

Again: T wave changes (ischemia), then

a higher rate with more chaotic switching between

pacemakers. MAT is associated with COPD, hypoxia,

2) S T-segment changes (injury), and then

digitalis,

3) Development ofQ waves (cell death)

theophylline,

severe

hypokalemia,

and

hypomagnesemia. Atrial rate is 100-130 bpm. The rhythm is "irregularly irregular." Sinus

pauses

result

long

interval.

ectopic escape beat (different P wave) may pre

LOCATION OF Ml vs. ECG CHANGES Left ventricle: •

Septal MI

pacemaker takes over the rhythm, the rate is usu

•

Anterior MI =V3-4

ally 60-80 bpm. If a junctional pacemaker focus

•

Anteroseptal MI

•

Lateral MI=I, aVL, V5, V6

•

Anterolateral=I, aVL, V3-6 (if V1-6=extensive

•

Inferior MI

•

Apical MI =II, III, aVL and any of V1-4

cede the

resumption

of the

rhythm. If

atrial

takes over the rhythm, this is termed a "junctional (escape) rhythm." With a junctional rhythm, there is a change in the P wave-it may not be visible

40-60 bpm.

changes in V1-2

V1-4

anterolateral MI)

or it may be a retrograde P wave very close to the QRS (short PR interval). Junctional rate is normally

II, III, aVF

THE ELECTROCARDIOGRAM

REMEMBER ...

5-67

REMEMBER ... These ECG changes [Know!]: o

What are the ECG findings with A-fib?

What are the ECG findings with MAT?

What are the ECG findings with a PVC?

Describe the sequence of ECG changes with

dofetilide), hypocalcemia, hypomagnesemia, and

the different phases of an MI.

CNS insult. This is a precursor to torsades de pointes.

tis, drugs, metabolic abnormality, and CNS insult (intracerebral hemorrhage). o

What ECG changes occur with a septal Ml?

What conditions can cause diffuse inverted

What conditions can cause a prolonged QT?

What type of Ml is AV node dysfunction

Large U waves are associated with hypokalemia,

A low-voltage ECG tracing is associated with pericar

AV node dysfunction is associated with an inferior MI

bradycardia, and digitalis toxicity.

and with digitalis and verapamil toxicity.

What conditions cause resting ST elevation?

I, a VL

Right ventricle: o

is fairly sensitive and specific for RV infarction

90% each). It is diagnostic of RV infarction if the

ST elevation is greater in V4R than in Vl -3. o

With the standard ECG, suspect an RV infarction if, with an inferior infarction, there is also ST-segment

elevation in V1-2. Also be suspicious in the instance

9 ri 9

where you see ST-segment elevation in VI, along with ST-segment depression in V2!

NOTES

With acute inferior MI, there may be reciprocal ST

h ta

depression in septal leads (Vl -2). With an anterior/septal MI, there may be reciprocal ST depression in the inferior leads.

•

What causes ST-segment elevation during a stress

•

What causes resting ST elevation?

test? Stress-induced coronary artery spasms.

Acute MI

Post-MI wall motion abnormalities in the infarcted areas

right precordial leads. ST elevation in V4R to V6R �

Bifascicular block, in contrast, is associated more

RV infarction is best determined by placement of the

(

V d ti e n U •

with anteroseptal MI and calcific aortic stenosis.

Posterior MI =tall R in Vl -2; ST depression in Vl -2 High lateral MI

G R

dia! effusion, hypothyroidism, obesity, and COPD.

associated with? What about bifascicular block? o

Peaked T waves: hyperkalemia. (If severe, ECG looks

T waves? o

Prolonged QT: drug effect (quinidine, sotalol,

like a sine wave.)

Anterior? Lateral? Know all these! o

Diffuse, inverted T waves: ischemia, pericardi

The trick for reading the ECG with a suspected acute posterior MI is to hold the ECG upside-down and back wards, while holding it up to a light to see the tracing.

Spontaneous spasm of the coronary artery

Pericarditis

ANALYSIS

Analyzing the ECG:

First, check the rate and rhythm. Next, check the intervals-especially the PR, QRS, and QT. Then, check waveforms. The ECGs on the following pages give you a little practice. Figure

5-11

provides

memory

aid

for

ECG

interpretation. This memory aid is copied below each ECG on the following pages. Table 5-14 and Table 5-15 summarize the information in the ECG section of the text.

Study Vl-2. A posterior MI assumes the morphology of

Study tip: To the top left of each ECG is the presenting

other Mls with this trick. (R waves look like Q waves

information. The bottom-left notes are the main find

and ST depression appears to be ST elevation.)

ings. So do not look at the bottom information until you

Posterior MI is often associated with inferior- and lateral-wall Mis. So, if you see either of these, look closely for signs of a posterior MI. Signs of acute infarct and ischemia signs may be obscured by pacemakers.

LBBB, WPW, HCM, and ventricular

have done your reading of the ECG!

m 0 G') (/)

5-68

ECG INTERPRETATION

Rate QTc

QT/j(R-R)

Waveforms:

Rate -----Rhythm

E18

I ,500/#mm or 300/#large squares

Pwave ------QRS voltage

_______

ST segment

___ _

QTc

__ _

Rwaves ------

Intervals: PR ------QRS

__ _

QRS axis/shape

Twaves

____

G R

______ _

-------

u waves

------

V d ti e

Figure 5-11: Memory Aid for ECG Interpretation

n U -

Table 5-14: ECG Summary Table (1 of 2) Normal Heart Rate

Heart Rhythm Intervals and

Durations

9 9

1 )HR

;; - },

h a

2) Rhythm

Abnormal

Common Causes

<60bpm

100bpm

Sinus tach, A -fb i with rapid V response, V-tach, SVT

1 50bpm

Rule out atrial flutter with 2:1 AV Block.

NSR

Many

Multiple (see text)

l2�200 ms

< 120 ms

Shorter than 120 ms (3 �iv(delta wave)

all squares) may indi�ate:

Junctional rhythm (with'retrograde P wave)

Left atrial overload l st degree AVblock

� wPW if the PR intlfval is shortened Wntficular ectopy or pac��aker

ABerrant conduction (BBB,r

Drugs; tricyclic overdose,(a1so causes long QT)i'\ "'

340-450 ms

(men)

340-470 ms

(women)

450 ms

(men) >

470 ms

(women)

' ; m-::s&

-"-�

Hypocalcemia lengthens ST segment

Hypokalemia (often w/large U waves)

Type Ia (quinidine) and III (amiodarone) antiarrhythmics Tricyclic overdose (also causes long QRS)

Intracranialbleed (also causes inverted Ts) � , Hypercalemia

Digitalis effects (which also o;ften causes a scooping of the

ST segt!lent)

)r('

ECG INTERPRETATION Table 5-15: ECG

Waves and Segments 6)P wave

5-69

Summary Table (2 of 2)

Abnormal > 2 mm,> 120 ms

Common Causes Tall, peaked P waves in II suggest right atrial overload Biphasic in VI and broad and notched in II suggest left atrial overload

Decreased

Severe hyperkalemia

7) Q waves

In ant or inf leads

Acute: More severe MI

8)QRS

High

LVH (SVI + RV5> 35 or RV6> 25-35)

Low

1) Pericardia! effusion 2) Tamponade 3) Emphysema 4) Obesity 5)Amyloid

Right:>+110

Right axis may be seen in:

voltage

9) QRS axis

I) Normal in children and young adults 2) LPFP (+80 to+ 140)

Left: <-30

3) RVH

4) RV overload (pul HTN, PE)

Left axis may be seen in: LAFB and LBBB

G R

1) lntrinsicoid deflection> 50 ms with some LVH

10) R wave

2) Delta wave with WPW; V1 shows RR' or RSR' with RBBB 3) Large R in I with LBBB and LAFB 4) Large R in inferior leads with LPFB

V d ti e n U

5)R in V1, V2 with posterior MI

6) Six causes of Tall R wave in V1: RVH, RBBB, WPW with delta wave, Posterior Infarct, Duchenne's muscular dystrophy, Dextrocardia 1) S wave in V6 with RBBB

II) S wave

2) Large S waves in inferior leads with LAFB

3) Large abnormal S waves in lateral leads (1, a VL) with LPFB 12)ST segment

Elevation

1) Diffuse: acute pericarditis or myocarditis

2) Localized means MI, transmural ischemia, or wall motion disorder: Area involved:

1) Septal= changes in V1-2 2)Anterior MI = V3-4

3)Anteroseptal MI = V1-4

4)Anterolateral =I, a VL, V3-6

(if V1-6 also, then= extensive anterolateral MI)

Depression

9 9

5) Lateral MI =I, a VL, V5, V6 6) Inferior MI =II, III, a VF

1) Subendocardial ischemia (esp if downs! oping or flat) such as seen in classic angina 2) ST depression V1-2 with acute posterior MI

3)Reciprocal depression V1-2 with some inferior wall Mls-esp. those w/ lateral posterior extension; also, conversely, reciprocal ST depression in INFERIOR leads

1 3) T wave

h a

Tall, peaked

Inverted

with some ANTERIOR Mls

4)Dig toxicity 5) LVH 6)hypokalemia

LV strain (ST depression with flipped precordial

T waves) 8)RVH with RAD and ST depression preceding a flipped T wave in Vl

Hyperacute MI (usually with ST elevation and sometimes Q waves)

T hese are followed in time by a more prolonged T wave inversion

2) Hyperkalemia (early sign-followed in time by widened QRS and deer. P wave, prolonged QRS, and AV conduction problems) 3) Intracerebral hemorrhage 4) Common in Vl-2 with evolving posterior MI

1) Post hyperacute MI (see above)

2) Severe ischemia (may have prolonged QT)

3) Post resuscitation

4) Pericarditis

5) Intracranial bleed can cause deep inverted T waves (along with prolonged QT) 6) In lateral leads (I, aVL, V6) with LBBB

7) In septal leads ( VI-2) with RBBB and

LVH

8) ln Vl with some RVH (suggests RV hypertension) 14) U wave

> 1 mm, positive (nl)

Indicates increased susceptibility to torsades de pointes

2) Drugs: Type Ia (usu w/prolonged QT ) 3) Hypokalemia: (usu w/prolonged QT)

Negative

l) HTN 2)AV valve disease 3) Major ischemia 4)RVH 5) Up to 60% of patients with an anterior MI 6) Up to 30% of patients with an inferior Ml

7) Up to ÂŠ 2014 MedStudy

30% of angina patients

m 0 G') fl)

5-70

ECG INTERPRETATION

Case

I: A 57-year-old man

with previous myocardial infarction and chronic hypertension on digoxin,

r..

Ill'- I-

�� \.

VI \.

beta blockers, and ACEI.

II.

I I

I J

II r-

I !

I·

Note I'' degree AV block with P-R of 340 ms. Left ventricular hyper

Rate

trophy. Probable early repolarization-the sharp S wave

Intervals: PR

QTc

ischemia.

2: A 36-year-old man

9 9

and "slow heart rate" since

his teens.

r i h I-I

ta Note sinus rhythm with Mobitz type

2 second-degree 2: I AV block. This initially looks like Mobitz 2, but there is a subtle increase in the PR interval and this also has a narrow QRS complex (Mobitz 2 usually has a wide complex).

__ _ _ _

QRS

repolarization. Possible inferior

___ _

__ _ _

U -

____ _

QRS voltage

__ _

QRS axis/shape

R waves

ST segment

T waves U waves

___ _

_ ___ _

_ ____

I I I V\

____ _

It\

r--

Pwave

t i n

_____ _

in V4-5 enhances the likehood

with history of cocaine abuse

d e

Waveforms:

__ __ _ _ _

Rhythm

of the ST segment being due to

Case

G R V

I !

Ill

I�

Rate

Waveforms: _ _____ _

Rhythm

Pwave

___ _

.,--QRS voltage

_ _____

Intervals: PR

R waves ____ _

QRS QTc

___ _

__ _

QRS axis/shape ST segment T waves U waves

____ _

___ _

____ _

ECG INTERPRETATION

Case 3:

A 76-year-old man

with chronic heart failure.

[/\

!"'

!---

aVR

Note second-degree Mobitz type I (Wenckebach) 3:2 AV block. The

�

·-aVL I

first P wave is visible, the second is

Ill

just peeking out of the previous T

aVF II

and "slow heart rate" since he was young.

9 ri 9

h ta

___ __

llf 4

IV I

·� � .· · .·VL . _

II\>' '

Ill

aVF

1-\.

U waves

aVK

3'd degree AV block.

ST segment ____

T waves _____

f--.

_ __ _ _

II Ul

Note sinus rhythm with complete,

R waves

II Ill

Ill

i'! IV

QRS voltage ___

QRS axis/shape

QTc ____

Ill

Pwave _____

QRS ____

previous T wave. Possible COPD.

m 0 G")

Waveforms:

Rate _______

wave, and the third is fused with the

with history of drug abuse

V d ti e n U

Rate

__ _ _ _ __

Rhythm ______

Intervals: PR _____ QRS ____ QTc ____

G R

Intervals: PR _____

A 36-year-old man

D 11\:1.7 I U Jv, II

Rhythm ______

I ., I

y[ll

I I

f---

[;;;

t-t-

Iii

Case 4:

5-71

r._

Waveforms: Pwave _____ QRS voltage

QRS axrs/shape R waves _____ ST segment _ ___ T waves U waves

____ _ _____

I\..

5-72

ECG INTERPRETATION

Case 5:

A 54-year-old

woman with history of chronic smoking.

,_.,

a[R

,......

f'-.

r---1-''-r-

rv-

-�

G R

Note sinus rhythm with right axis

V d ti e Pwave

deviation and incomplete RBBB pattern.

6: A 77-year-old man

with a history of chronic

9 9

congestive heart failure.

r i h

1-'

h I'-

R waves _____

ST segment ____ T waves _ _ _ __

n U QTc

_ __

QRS axis/shape

--.,--QRS ____

consistent with pulmonary disease

___ _

U waves

____ _

1\ I

1\ \ f-

1\.

I II

j...l

1-J

1--'1\. riJ

..1.

____ _

QRS voltage

_ __ __ _

Intervals: PR

!All'

Waveforms:

_______ _

Rhythm

I -v

!1\

Rate

iti

Case

41v

""-

[\:

1'-

I'-

r-'

I il

I !I

�

(

Note sinus rhythm with complete LBBB and left atrial enlargement. This LBBB is a little atypical, but notice the large slurred S in the anteroseptal leads and the T wave opposite the mean QRS in the anterolateral leads. Also notice the terminal portion of the QRS in Vl-3 is slurred-also consistent with

aVR

�

II\;[

III

aVF

Rate

_______ _

Rhythm

______ _

Intervals: PR

::------

QRS QTc

____

_ _ __

LBBB.

Waveforms: Pwave

_ ____

QRS voltage

__ _

QRS axis/shape

R waves ___ __ ST segment

_ ___

T waves _____ U waves

____ _

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

5-73

EGG INTERPRETATION

Case 7:

A 67-year-old man

with a history of a cardiac

1' -

murmur and prior repair of a

congenital heart defect.

/"\

.n IN

IN 2

IT Ul IV

1n v

1,...[\. 1---UVI'-

+- U\V

aVR

��

Rate

fl\/

Ill

aVF

Intervals: PR

Note sinus rhythm with RBBB.

Ill

1-- 11

fA-f../

8: A 77-year-old man fl Il l

infarction and recurrent

9 9

syncope.

r i h h

1T 1'-

!-J'r

R waves

I I

Ill IU II

T waves

_ __ _

_ ____

!'-

II \.

____ _

U waves

Ill

1'/1 L1--- f--..J l.r-

__ _

_ ___ _

ST segment

___

____

1-r

lr-

Ill II

lFf Il l 10

Note sinus rhythm, I'' degree AV

aVR

)\9 · .,

�VL

il ...._/

block, RBBB and left anterior fascicular block (bifascicular block). Note also Q waves from VI to V4 consistent with anteroseptal infarct.

____ _

QRS axis/shape

____ _

QTc

Case

Pwave

QRS voltage

�U\.

Waveforms:

_ ____ _

QRS

with a history of myocardial

V d ti e n U

_____ _

Rhythm

G R

11\.

m 0 (j')

Ill

aVF

Rate

Waveforms: _ _ ____ _

Rhythm ------

Intervals: PR

P wave

---.,.QRS voltage

__ _

QRS axis/shape R waves

____ _

QRS QTc

___

___ _

ST segment T waves U waves

____ _

___ _

_ ____

_ ___ _

Ill

ECG INTERPRETATION

5-74

Case

A 65-year-old man

with recurrent palpitations. l'l

1"-

til

tIL 1 1'

lA r\

r4 r----

n r--.A\]\ a

Jll/1-

1--

Ill

lr-'

f-""

Jl 5

II i-1

h lA \.

r--

V \1!

1:�

I! fJ\

Rate

lA \.

r--

A ��, 1-'\. f- 1'--��r

Intervals: PR

ventricular premature beats in bigeminy. Note the full

QTc

compensatory pause after the PVC.

ll) I

Pwave _____ QRS voltage ___ QRS axis/shape __ R waves

_____

QRS

II i- Wl

Waveforms:

_ _ ______

Rhythm ______

Note sinus rhythm with frequent

I-"'

r-'lr'

I"-

____ _

ST segment

___ _

T waves

___ _

U waves

_ ___

____ _ _____

Case I 0: A 45-year-old man with a history of rheumatic fever as a child and cardiac

I I

I�

murmurs.

II I

:II

I II

!av

Ill

in the inferior-lateral leads.

aVF

Rate ________ Rhythm

_____ _

Intervals: PR

I�

I 1-' l v:

Lr-.

.II

aVR�)f7 Note atrial fibrillation and flipped Ts

lr-'-

�·

Waveforms: Pwave

____ _

QRS voltage ___ QRS axis/shape __ R waves _____

___ _ _

QRS

__ _ _

QTc ____

ST segment

_ _ __

T waves _____ U waves

____ _

ECG INTERPRETATION

Case

II: A 44-year-old

man with a history of

I I J L

HJ'

2-pack-per-day smoking for

5-75

1!.

15 years.

"''

"'r'-o

I I I.'(\('.N('-,''-f"..N (\... N '\

I IJI,

Rate

n I'\I'll

I '\ii'Y� V I'\/'\/I"V"

QTc

A 34-year-old man

with history of palpitations

1111 I I�I

Pwave

v�

QRS axis/shape R waves Twaves U waves

____ _

____ _ _____

(\ Ill"

-�

A I� L

f.-"

r--

I' w r

1'-

I I I. :ir

Ia,iF

.)\

I r

1-"r

f.-

1'-'

r--

I Note sinus rhythm, short P-R interval, and delta wave consistent with Wolff-Parkinson-W hite syndrome. This is one of those ECGs on which you may mistake the delta wave for prolonged intrinsicoid deflection (as seen with LBBB and LVH) until you check the PR interval and find it is short!

avR�Ft Il aVF I

Rate

_______

Rhythm

______

-Intervals: PR =-QRS QTc

___ _

_ __ _

v'lv"

ST segment ____

___ _

rh J

In IV'VIY

m 0 (j)

____ _

since childhood.

l!--

QRS voltage _ __

_ __ _

Ir--'

vv�v

!.[.!'

�f..-

Waveforms:

RBBB.

Case 12:

Ill

rvrv1V

Intervals: PR _____ QRS

1---Jr r""1r-

______

vertical axis, and incomplete

rm' II

_______

Rhythm

Note atrial flutter with 4: I block,

41'

r-<

Waveforms: Pwave c----QRS voltage

_ __

QRS axis/shape R waves

ST segment T waves U waves

__ __ _ ___ _

____ _ _____

(II

5-76

ECG INTERPRETATION

Case

13: A 74-year-old

woman with recent episodes

r-I

of light headedness and

a rll

t'--\1/\.�1

hi'"'- r-

1"-1

V\. r--

palpitations.

II'

� I�

�

U; If-

f.1 J;1

Vfll. A

f--1 �I

III

�

!A.

III

I'-'

-A � lA

Note narrow QRS tachycardia with retrograde P waves evident in precordial leads VI and V2 consistent with AV node

Rate

oVR��L

reentrant tachycardia at a rate of

Rhythm

approximately 150 bpm. Also

Ill aVF II

pronounced ST-segment depression in the inferio-lateral leads-it is

Pwave _____ QRS voltage _ __

_____ _

Intervals: PR

QTc

in the ischemia.

QRS axis/shape __ R waves

_____

QRS

likely that the rapid rate is a factor

Case 14:

Waveforms:

______ _

____ _

ST segment

____

___ _

T waves _____

_ _ __

U waves

_____

A 71-year-old

man with history of previ

I I�

ous myocardial infarction

IJ\ '\ J

1\!

and coronary artery bypass

�

1\ I I .I II

II \

surgery admitted for chest pains and syncope.

_/ :r

I II\ 1"\ r y

\ II v

I \1

I,JI\

1 \o I 'I II I II II\ a�

1\ 1\ 1/\ 111 \ 1\ II \ 1\. II I II J \ IV

A lA

I'I

� II IJ'

II II \. \1

rJ I \ \ 011 1\, I IV v �

II\ 1\ ( IJ \ v

�

\I ( II \

\ I

1\ I

I' If\

Note the wide QRS tachycardia with negative concordance in the precordial leads consistent with ventricular tachycardia.

Rate _______ Rhythm

_____ _

Negative concordance is the QS pattern throughout the precordial

Intervals: PR _____

leads; there is no hint of R wave

QRS

progression.

QTc ___ _

___ _

Waveforms: _ Pwave ____

QRS voltage _ __ QRS axis/shape __ R waves

_ ___ _

ST segment ____ T waves U waves

___ _ _ ___ _ _

ECG INTERPRETATION

Case

5-77

15: A 47 -year-old man

with Type I diabetes and chronic renal insufficiency

I I

admitted with diabetic

Ill A .ft)\

�r--- nr -JI

I V I

'\._

l t"'1r- � II V

II 1\

f.l\ II

)

II ' II ' \ \)

ketoacidosis and serum potassium of7.

II A I I III 1'-'Uv 'V r:w

I"'

II A II 1\

I I� I 1\

" VR

lA 'I

� fl\

Ill

aVF

II '\ ) rr

) I-

,il

1 n lu'

II lA

(/)

!V il./lr

QRS QTc

'\J

---

Pwave .,-QRS voltage

__ _

QRS axis/shape Rwaves

_ _ __

ST segment ___

____

Twaves

___ _

__ __

U waves

with hyperkalemia.

Case

jV'

Waveforms:

____

LVH by voltage criteria consistent

m 0 G')

Note tall and peaked T waves.

II lA ) II\ 1l ) V6

______

Intervals: PR

I' 1\ jl V "' I '-�� v

�1-

Rate _______ Rhythm

1'-'

_ ____

16: A 39-year-old

woman successfully

rv-

resuscitated from ventricular

fibrillation with no evidence of acute myocardial infarction.

J�

f/ II

1---

aVl

i-VIf-"i'-

��

lA I

i'-1\J�r-- II-

t"-i·t II

,__

[IV

"VR

Note prolonged QT of 530 and a

�•�

the leads and choose the longest QT interval-in this case, use lead V2.

Rate

_ _ _____

Rhythm

QTc of 640 ms. When measuring the QT interval, you must look at all

Ill

aVF

_____ _

II Intervals: PR =---QRS QTc

___ _ __ _ _

Waveforms: Pwave

____

QRS voltage

__ _

QRS axis/shape Rwaves

____

ST segment ___ Twaves ____ U waves

____ _

I J�V

5-78

ECG INTERPRETATION

Case 17: A 65-year-old man admitted for pleuritic chest

_I J

pains I week following a bout of flu-like symptoms.

I II

I r-

!IL�

\12

th 'I

·'"

I"-

�,

1'- I"'H"

WI-

Waveforms:

Rate ________

ote diffuse ST-segment elevations consistent with pericarditis. There is

P w ave ,------

QRS voltage _ __

_ Rhythm ___ __ _

PR segment depression best seen in II also often seen with pericarditis.

QRS axis/shape __ R waves _____

Intervals: PR =-----

Also note the concave up ST

QRS

segment elevation more consistent

QTc

ST segment ____

___ _

T waves _____

____

U waves

with pericarditis than MI.

Case

18:

__ __ _

A 65-year-old

man admitted with a 2-hour episode of severe retroster

I ! I I

nal chest pains and shortness

II I

r---

�tR

I"-

of breath.

IIJ

1'\ v.

1'-

I" \.

Ill r-

Ill I ll

;v:

hi'

Rate ________

Note marked ST-segment elevation in precordial leads consistent with acute extensive anterolateral infarction. Associated

Rhythm

__ ____

Intervals: PR

=------

QRS QTc

___ _

__ _ _

T waves are hyperacute.

I I

II I

IJL r--

,._,

Waveforms: ---.,-QRS voltage ___

P wave

QRS axis/shape R waves

____ _

ST segment

_ ___

T waves _____ U waves

_____

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

ECG INTERPRETATION

Case 19a: An 80-year-old

:�

woman is seen in the emergency department

�

f--

·r

i1/I

J, V2

��- ,.>-.! •u ' ,\.

r--

1-Ji

5-79

II II /\

..)'f I

hours after waking up with severe retrosternal pressure and lightheadedness.

I I

r-.

N�'"'II

"-f--A

l/1

a\IL

! Jl

Yl5

HI?J

. I

-r

¥b

� -;;_;r

1'-

�·

-'I

1"-'

I'IV,

r-----'

I h

I I

I"--f.-

I-'

M- 1'-,..-.' v

Vol\- i-f--'

f--

�ll I

Note ST-segment elevations in the

Waveforms:

Rate _______

---.,QRS voltage ___ P wave

precordial leads consistent with acute anterolateral STEM I. Even

Rhythm _ _____

though the ST segment is mildly

Intervals: PR

concave up, the lack of an S wave

QRS

in V 4-5 makes early repolarization

____ _

ST segment ____

___ _

QTc

unlikely-as does the presenting

QRS axis/shape R waves

_ __ _ _

T waves

U waves

___ _

___ _ _

____ _

complaint!

Case 19b: 20 minutes following infusion of a

lr """II

thrombolytic, a repeat

ECG is performed.

1vR

I I'

f--�

I\/

/'1..

i-1 n lr H-

Jo II

Iii

10. v

I/\

.lil

J-

aVI!.

90 bpm. Note change in QRS duration and axis shift with retrograde P waves-showing a

V-A association (i.e., the ventricle is resetting the atrium!).

MedStudy

r II

I\/

LLI

If\.

\1 I I

1/ I

y (\

;-,.

r-,,.f [---,/ rf--

"slow" ventricular tachycardia at

Shows accelerated idioventricular

�n

H-

rhythm (reperfusion arrhythmia) or

lA I \I

'7-

Rate

f--

(

VIi

I'-

_____ _

Intervals: PR

1'-- /I'- I/

'II

Ill

P wave ---,.QRS voltage ___ QRS axis/shape __ R waves _____

____ _

QRS QTc

___ _

I I'-

U I IV

Waveforms:

Rhythm

/j I

___ ___ _

ST segment T waves

U waves

_ ___

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nausea, and vomiting of 2-hour duration.

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ote acute inferior infarction with reciprocal ST segment changes in the right precordial leads and complete AV block shown by AV dissociation with an atrial rate of 75 and a ventricular rate of 40.

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_ ____

FOR FURTHER READING

FOR FURTHER READING [Guidelines in blue)

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THE ELECTROCARDIOGRAM ECG Wave-Maven. http://ecg.bidmc.harvard.edu/maven/ma venmain.asp Mirvis OM, Goldberger AL: Electrocardiography, in Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, ()!" ed, RW Bonow, et al (eds). P hiladelphia, Saunders,

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Rheumatology 6- I

INFECTIOUS ARTHRITIDES .......................................................6-28

OVERVIEW .................................................................................. 6-1

SEPTIC ARTHRITIS ..................................................................6-28

ANTINUCLEAR ANTIBODIES .................................................6-1

Overview ................................................................................. 6-28

LABS

................................................... ...............................................

ANA. .......................................................................................... 6-1

Gonococcal Arthritis ............................................................... 6-29

Specific ANA Te sts ................................................................... 6-1

Nongonococcal Arthritis ......................................................... 6-29

ANCA ............................................................................................ 6-2

A cute Rhe umatic Fe ver .......................................................... 6-29

COMPLEMENT............................................................................ 6-3

WHIPPLE DISEASE ..................................................................6-30

RHEUMATOID FACTOR AND ANTI-CCP ............................... 6-4

TUBERCULOUS ARTHRITIS ..................................................6-30

MAJOR HISTOCOMPATIBILITY COMPLEX: HUMAN

VIRAL ARTHRITIS .................................................................... 6-30

LEUKOCYTE ANTIGENS ....................................................... 6-4

LYME ARTHRITIS .....................................................................6-30

HLA-B27 ................................................................................... 6-4

LESS COMMON ARTHROPATHIES ....................................... 6-31

HLA -DR2, 3, 4 .......................................................................... 6-4

A dult-Onse t Still's Disease ..................................................... 6-31

ERYTHROCYTE SEDIME TAT!ON RATE AND C-REA CTIVE PROTEIN .......................................................... 6-5

He mochromatosis Arthritis ..................................................... 6-32 Neuropathic Arth ropathy (Neuropathic Joints) ...................... 6-32

THE JOINT ........................................................................................6-5

Hypertrophic Pulmonary Oste oarth ropath y ...........................6-32

SYNOVIA L FLUID AND CRYSTA L ANA LYSIS ..................... 6-5

Post-Streptococcal Reactive Arthritis ..................................... 6-32

IMAGING STUDIES .................................................................... 6-6

OTHER CONNECTIVE TISSUE DISEASES ...............................6-33

GENETIC COLLA GEN DISORDERS ............................................ 6-6

RAYN A UD PHENOMENON .................................................... 6-33

RHEUMATOID ARTHRITIS ............................................................6-6

MIXED CONNECTIVE TISSUE DISEASE ............................. 6-33

OVERVIEW .................................................................................. 6-6

lgG4 RELATED DISEASES ......................................................6-34

SIGNS I SYMPTOMS OF RA ......................................................6-7

ANTIPHOSPHOLIPID SYNDROME............................................ 6-34

EXTRAARTICULAR MANIFESTATIONS ............................... 6-8

SJOGREN SYNDROME.................................................................6-34

TREATMENT OF RHEUMATOID ARTHRITIS ....................... 6-9

SYSTEMIC SCLEROSIS I SCLERODERMA ..............................6-35

NSAIDs ................................................................................... 6-10

TYPES OF SYSTEMIC SCLEROSIS .......................................6-35

DMARDs ................................................................................ 6-10

Diffuse SSe(- 20%) ...............................................................6-35

Biologic Age nts ....................................................................... 6-12

Limited SSe(- 80%) ............................................................... 6-35

Immunosuppre ssants ...............................................................6-13

Systemic Sclerosis Sine Scleroderma ..................................... 6-36

Misce llaneous .......................................................................... 6-14

MANIFESTATIONS OF SSc ...................................................... 6-36

SYSTEMIC LUPUS ERYTHEMATOSUS .................................... 6-14

SSe: Skin .................................................................................6-36

MANIFESTATIONS OF SYSTEMIC LUPUS .......................... 6-14

SSe: Joints ............................................................................... 6-36

SLE: Joints .............................................................................. 6-14

SSe: Muscle s ........................................................................... 6-36

SLE: Skin and Mucous Me mbrane s ....................................... 6-14

SSe: Lungs .............................................................................. 6-36

SLE: Lung ............................................................................... 6-15

SSe: Kidney .............................................................................6-37

SLE: Heart ...............................................................................6-15

SSe: GI ....................................................................................6-37

SLE: Kidney ............................................................................ 6-15

SSe: Heart ................................................................................6-37

SLE: Blood ..............................................................................6-15

TREATMENT ..............................................................................6-37

SLE: CNS (Ne uropsychiatric Lupus) .....................................6-16

EOSINOPHILIC FASCIITIS ...........................................................6-38

DIAGNOSIS ................................................................................6-16

INFLAMMATORY MYOPATHIES ...............................................6-38

SLE AND PREGNANCY ...........................................................6-16

POLYMYOSITIS AND DERMATOMYOSITIS ......................6-38

PROGNOSIS ............................................................................... 6-17

Polymyositis ............................................................................ 6-38

TREATMENT OF SLÂ£............................................................... 6-17

Dermatomyositis .....................................................................6-38

DRUG-INDUCED LUPUS ........................................................ 6-17

Antisynth e tase Syndrome ....................................................... 6-39

SERONEGATIVE SPONDYLOARTHRITIS ................................ 6-17

Diagnosis of PM and DM ....................................................... 6-39

ANKYLOSING SPONDYLITIS ................................................ 6-18

Cancer in PM and DM ............................................................ 6-39

Overview ................................................................................. 6-18

Treatment of PM and DM ....................................................... 6-40

Diagnosis .................................................................................6-18

INCLUSION BODY MYOSITIS ...............................................6-40

Treatment .................................................................................6-19

COLCHICINE MYOPATHY INEUROPATHY ........................6-40

REACTIVE ARTHRITIS ............................................................6-19

DRUG-INDUCED MYOPATHY ...............................................6-40

Overview ................................................................................. 6-19

NONARTICULAR RHEUMATISM .............................................. 6-40

Treatme nt.................................................................................6-20

FIBROMYALGIA .......................................................................6-40

lBO-ASSOCIATED ARTHROPATHY ...................................... 6-20

MYOFA SCIAL PAIN SYNDROME .........................................6-41

PSORIATIC ARTHRITIS ........................................................... 6-20

COMPLEX REGIONA L PAIN SYNDROME ..........................6-41

SUMMARY ................................................................................. 6-21

OTHER CA USES OF NONARTICULAR RHEUMATISM ....6-42

OSTEOARTHRITIS ........................................................................ 6-21

VA SCULITIS ...................................................................................6-42

CRYSTAL DEPOSITION ARTHRITIDES .................................... 6-23

OVERVIEW ................................................................................6-42

GOUT........................................................................................... 6-23

LARGE VESSEL VA SCULITIS ................................................6-42

A cute Treatment ...................................................................... 6-24

Overview .................................................................................6-42

Chronic Treatme nt...................................................................6-25

Giant Cell( Te mporal) Arteritis ...............................................6-43

Gout Pearls ..............................................................................6-26

Polymyalgia Rhe umatica ........................................................6-43

CPPD DEPOSITION DISEASE.................................................6-26

Takayasu Arteritis .................................................................... 6-44

HYDROXYA PATITE ARTHROPATHY ................................... 6-27

Aortitis ....................................................................................6-44

MEDIUM I SMALL ARTERY VASCULITIS Polyatteritis Nodosa

...........................

6-44

....... . . . . . . . ....... . . . . . .............................. . . . . . . . .

6-44

Eosinophilic Granulomatosis with Polyangiitis (a.k.a. Churg-Strauss Vasculitis) Granulomatosis with Polyangiitis Microscopic Polyangiitis

6-45

.... . . . . . . . . . . . . . .................. . . . ....

......... . . . . . . . . . . . . . . . . . .. . . . . . ..........

6-45

. . ................... . . . . . . . . . . . . . . . . . . . . . . .............

6-46

OTHER SMALL-V ESSEL VASCULITIDES

. . . . . . . . . . . . . . . ............

6-46

....... . . . . . . ....................... ........ . . . . ......

6-46

Hypersensitivity Vasculitis

Henoch-Schiinlein P ur pura (lgA Vasculitis) Cryoglob ulinemia

.. . . . . . ...... . . . . . . . . . . . . .

6-47

. . ........... . . . . . . ........ . . . . . .............................. . . . . . .

6-47

ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE I GOODPASTURE SYNDROME BEH<;ET DISEASE

6-48

.........................

6-48

. . . . . . . . ..... . . . . . . . ....... . . . . . .......................... .. . . . . . ...

RELAPSING P OLYCHONDRITIS

.......................... . . . . . . . . . . . . . . . . .

6-49

RHEUMATOLOGIC ISSUES ASSOCIATED WITH MALIGNANCY AND DIABETES MELLITUS PAGET DISEASE AMYLOIDOSIS

6-49

. . . . . ..................................... . . . . . . . ..................... ... . . . . .

6-49

OFFICE ORTHOP EDICS OSTEOPOROSIS BURSITIS

Hand Hip

6-50 6-50

...... ................... . . . . . . . . ....... . . . . . . . . . ............ . . . . . . . . ...............

6-50

Shoulder Wrist

.......................... . . . . . . . . . . .. . . . . . . ........... . . .. . . . .

......... . . . . . . ................... . . ........ . . . . . . . . . . . . . . . . . . ..........

JOINT PAIN Elbow

6-49

.... . . . . . . . . ............

. . . . ........ ................ .. ............ . . . . . . . ....................... . . . .

....... . . . . . . . . . . . .. . . . . . . ........ . . . . . . ................ . . . . . . . . . . . .............

....... . . . . . . . . . ................................ ...... . . ................ . . ........

Foot

6-51

...... ...................... . . . . . ......................................................

6-53

. . . . . . . . . . . ........ . . . ............ . . . . ......... . . . ... .............. ...... ...............

6-54

.................. . . . . . . ........... ............... . . . . . . ..................... . . . . . . . . . . .

6-54

.... . . . .... . . . ....... . . . . . . . . ....... . . . ......... . . . . . . . . ............. . . . . . . . . . .............

Knee

6-50

................... . . . . . . . . . . . . . . . . . . . . ........... . . . ......... . . . . . . . . ....... . . . . . . . . . ...

........... ...................... . . . ..................................... . . . . . . . . .........

LOW BACK PAIN

. . . . . . . . . . . ...... . . . . . ....... . . . . . . . . . ................................

General Approach to Lower Back P ain Muscle Strain

6-54 6-56 6-57 6-58

............................ ......

6-58

...... . . . . . . . . ...... . . . . ............. . . . . . ....................... . . . . . . . . .

6-58

Disk Herniation

...... . . . . . ........ . . . . ....... . . . . . . . . . . . . . . . . . ........................

6-58

Spondylolysis and Spondylolisthesis

......................................

6-58

Spinal Stenosis

......... . . . . ........................ . . . .... ............................

6-59

FOR FURTHER READING

. . ...... . . . . . . . ....... . . . . . . . . ..... .................. . . . . . . .

6-59

LABS

ANA titers are considered pos1t1ve only if > I:80.

LABS

Titers > I :320 are considered clinically relevant for autoimmune diseases. Some rheumatologic diseases that

OVERVIEW

are ANA+:

Know everything covered in this topic area about Labs! If this is your first time through the Rheumatology section, go over this topic several times before you

Drug-induced lupus (100%)

SLE (98-IOO%): Note that ANA-negative lupus is rare; so ANA is pretty useful for ruling out SLE!

continue. What you learn here will enable you to make o

better sense of lab references later in this section.

Mixed connective tissue disease (MCTD; 93-IOO%)

Limited systemic sclerosis and diffuse systemic

Sjogren syndrome (48-70%)

healthy individuals. The key is whether the test results

Polymyositis/dermatomyositis (60%)

match the clinical picture.

Rheumatoid arthritis (RA; 40%)

Remember:

single

blood

test

makes

any

sclerosis (60-90%)

rheumatologic diagnosis. For example, ANA can be positive in many non-rheumatologic diseases and in

To interpret a test result, it is important to understand

Example of ruling in vs. ruling out: The ANA is positive

the sensitivity and specificity of the test. Sensitivity is

in almost all patients with SLE (high sensitivity) but also

the proportion of those with a positive test result among

is positive in many other diseases (low specificity). So,

patients with disease; tests that are very sensitive are

a negative ANA test is helpful for ruling out SLE, but a

useful for "ruling out" the disease. Specificity is the

positive test is poor for ruling it in.

proportion of those with a negative test result among

The patterns found with fluorescent staining differ with

patients without disease; tests that are very specific are useful for "ruling in" the disease.

the various types of ANA patterns. These different ANA attack different points in the nucleus, causing various diseases. We now have tests (below) that identify these antibodies far more precisely than with fluorescent

ANTINUCLEAR ANTIBODIES

staining.

ANA Antinuclear

antibodies

(ANA)

are

autoimmune

antibodies that attack components of the nucleus. They are found in many autoimmune disorders. The most common ANA tests:

When the ANA is positive and you suspect a specific rheumatologic disease, order the more specific antibody subtypes (ANA profile). Know which diseases are also associated with specific subtypes (Table 6-1 on page 6-2). Again, the general ANA test is not specific enough to diagnose any disease, only to rule one out.

Indirect immunofluorescence

Enzyme-linked immunosorbent assay (ELISA)

Indirect immunofluorescence is more sensitive; ELISA

Specific ANA Tests

is less expensive.

Anti-clsDNA (in high titer) and anti-Smith (anti-Sm) are

Results are reported as titers (e.g., I:320), with a

very specific for SLE. If one or both of these are strongly

particular pattern when positive. Titers show the dilution at which the antibodies become

undetectable. It is shown in doublings: I :40, I:80, I:I60, I :320, I:640, etc.-so, the higher the titer, the more

antibodies in the serum. Patterns are determined

by looking at a specially

prepared fluorescent stain slide to ascertain where the antibodies attack the nucleus. There are 6 different patterns:

centromere,

diffuse,

homogenous,

rim and

peripheral,

nucleolar.

speckled,

While

ANA

patterns may provide some information, they do not identify the specific antibody present, nor are they specific for any particular disease. The homogenous and rim patterns can be observed in systemic lupus erythematosus

(SLE). Anti-centromere

patterns

are

suggestive of anti-centromere antibodies, which are seen with the limited form of systemic sclerosis (formerly known as CREST-calcinosis, Raynaud 's, esophageal dysmotility, sclerodactyly, telangiectasia).

ÂŠ 2014 MedStudy

positive, the diagnosis of SLE is strongly supported. However, patients with drug-induced lupus can have antibodies to anti-dsDNA (hence, they are ANA positive also). Anti-U1-RNP is very sensitive for MCTD but not

very specific because it can be seen in SLE and other connective tissue diseases. In general, absence of the antibody excludes MCTD. Anti-UI-RNP and antiÂ dsDNA are often seen together because they bind to related antigens known as epitopes. An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system. The term epitope is often used interchangeably when describing an antigenic component of a cell. The clinical significance of anti-ribosomal P protein antibodies is their specificity for the diagnosis of SLE. These antibodies have not been found in normal controls and are rare in patients with other autoimmune diseases. There are studies suggesting an association and/or predisposition with CNS and liver disease in

6-1

6-2

LABS

Table 6-1: Antinuclear Antibody Disease Assoc1at1ons Associated with:

Subclass

Antibody

Specific for SLE; an indicator of disease activity (as are complement levels)

Anti-dsDNA

Specific ANAs

and identifies SLE eatients with potential f�r significant renal dis,�ase. Absent in classic drUg-induced SLE; sometime.s develops in patj�nts treated with TNF inhibitors. Specific for SLE.

Anti-Sm

SLE, neonatal SLE; Sjogren's, and sometimes myositis. Usually not found

SSA(Ro)

in scleroderma; passively transferred from mother to baby --+neonatal heart block. DR3 is associated with SSA. SLE and Sjogren's; sometimes found in patients with +SSA. Also passively

SSB (La)

transferred from mother to baby

�

neonatal heart block.

Sensitive for MCTD; also found in SL.e-- usually in association with " antiSm or anti-dsDNA.

Anti-Ul-RNP

Drug-induced lupus and SLE. Mainly used to rule out drug-induced lupus

Antihistone

caused by procainamide, hydralazine, chlorpromazine, and quinidine. Limited scleroderma; identifies increased incidence of pulmonary arterial

Anti-centromere

hypertension and improved survival.

__,,..._...

.. ; .. . ��

Progressive systemic sclerosis; identifies increased incidence of interstitial

Anti-Scl-70

(Anti-topoisomerase

lung disease and reduced survival. Anti-Jo-1

, Antisynthetases

type of anti-synthetase antiboi:ly; associated with myositis;

identifies increased incidence of interstitial lung disease. Anti- SRP(signal recognition protein) is associated with cardiomyopathy and refractory to tr�afi1lent.

lupus patients. Do not confuse anti-ribosomal with

specific ANA antibody causing the "speckled" ANA

anti-ribonucleoprotein antibodies (not the same)!

pattern found mainly in SLE and Sjogren syndrome.

Antihistone antibody can be seen both in SLE and

drug-induced

lupus.

is very sensitive

The

antihistone

antibody

test

(> 95%) for drug-induced lupus

(DIL). Drugs commonly associated with DIL include: procainamide, hydralazine, chlorpromazine, isoniazid, sulfasalazine,

methyldopa,

quinidine,

minocycline,

and anti-TNF agents. The absence of the antihistone antibody effectively rules out DIL in patients taking any of these agents, with the exception of patients who are on anti-TNF therapy or minocycline. It is rare to see antihistone antibodies in patients on anti-TNF biologics or minocycline, even though they manifest symptoms

During

the

same

period,

serum

antibody

was

discovered in these patients, which was named anti-SSA (or SSA). These

2 antibodies turned out to be the same

antibody. So, these terms can be used interchangeably you commonly see them together; e.g., Ro/SSA, SSA (Ro). Similarly, SSB is identical to La and commonly seen as La/SSB or SSB (La). The "SS" in SSA and SSB stands for Sjogren syndrome. The most important thing to remember about Ro and La is their association with congenital heart block. Patients with SLE who are pregnant or who plan to become pregnant should be tested for Ro and La antibodies.

suggestive of DIL. Further information on DIL can be seen on page

6- I 7.

ANCA

Anti-Scl-70 (a.k.a. anti-topoisomerase

I) is specific

Anti-neutrophil cytoplasmic antibodies (ANCAs) are,

for progressive systemic sclerosis, formerly known

as the term indicates, autoimmune antibodies against

as diffuse scleroderma; it is present in

antigens in the cytoplasm of neutrophils. ANCAs are

75% of cases.

Its presence supports a diagnosis of a systemic, diffuse

markers for vasculitis, including drug-induced vasculitis

process (not a limited cutaneous one) and is associated

(Table

with progressive skin involvement, pulmonary fibrosis, and a higher mortality.

6-2).

It is thought that the vasculitis may be caused by the ANCA antibodies, which stimulate the release of lytic

Before going further, let's clarify the terms Ro and

enzymes from neutrophils.

La. Anti-Ro (or just "Ro") was the term given for the

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

LABS

rapidly progressive glomerulonephritis (RPGN), anti GBM

disease,

and

drug-induced

ANCA-associated

vasculitis.

•

The most common causes of anti-MPO+ drug-induced

What two ANA subtypes are specific for a diagnosis

ANCA-associated vasculitis are the anti-thyroid drugs

ofSLE? •

propylthiouracil (PTU) and methimazole. Many other drugs are much less commonly associated.

Anti-U1-RNP is a very sensitive indicator for what rheumatologic disorder?

•

In summary:

Which antibody is associated with drug-induced •

lupus?

•

Which drugs are associated with drug-induced

Churg-Strauss, pauci-immune RPGN, Anti-GBM, and

lupus?

drug-induced.

Which rheumatologic disease is associated

The sensitivity and specificity of these antibody tests

with a positive c-ANCA and anti-PR3? •

c-ANCA+ plus anti-PR3+: Think GPA. p-ANCA+ plus anti-MPO+: Think MPA, EGPA,

are, in general, not high enough for them to be used for

Name 2 diseases that are p-ANCA+ and

screening. P retest probability of the disease in question

anti-MPO+.

is important and should be considered before ordering ANCAs.

Two ANCAs are identified by their immunofluorescence (IF) pattern:

COMPLEMENT

I) c-ANCA: Antibodies are diffuse in the cytoplasm.

The complement system is comprised of a variety

2) p-ANCA: Antibodies are perinuclear.

These ANCAs can

then be

subdivided

based

the antigen, or epitope, they are directed against: anti-proteinase

(anti-PRJ;

PRJ

small

proteins

that

function

enhance,

complement, the action of antibodies and phagocytic

ANCA)

anti

cells. Hypocomplementemia is seen in SLE, vasculitis, rheumatoid arthritis, and infective endocarditis. There is more on the complement pathway in Allergy

myeloperoxidase (anti-MPO; MPO ANCA). Laboratories

& Immunology, Book 4.

determine

components can be decreased due to a genetic deficiency,

these

antigens

using

enzyme-linked

But

note:

Complement

immunosorbent assay (ELISA). This further analysis of

consumption

the ANCA helps you narrow down a diagnosis.

underproduction-as in eclampsia or

So again, we have

(hemolysis, elevated liver enzymes, low platelets).

2 ANCAs (c-ANCA and p-ANCA)

during

complement

activation,

that are further categorized, based on ELISA, into whether or not antibodies are directed against the PRJ or MPO antigens. (P roteinase 3 and myeloperoxidase are enzymes located in neutrophil cytoplasmic alpha granules.)

I) c-ANCA-anti-PR3 Table 6-2: ANCAs

2) p-ANCA-anti-MPO c-ANCA and anti-PR3 are p-ANCA and anti-MPO

are

strongly more

loosely

IFANCA

ELISA

p-ANCA

Anti-MPO+

Disease

while related.

PR3 antigens usually cause the diffuse pattern seen in c-ANCA+ IF tests. The combination of c-ANCA+ and anti-PR3+ is very specific for granulomatosis with polyangiitis (GPA; previously Wegener granulomatosis). nonspecific. Table 6-2 shows you that many diseases are p-ANCA+ (especially in the anti-MPO category). Further test any p-ANCA+ results with ELISA for anti-MPO antibodies. If a patient is anti-MPO+, think vasculitis: microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis

(EGPA),

Churg-Strauss,

MPA EGPA Churg-Strauss Pauci-immune RPGN Anti-GBM disease

p-ANCA is less helpful because this IF pattern is

pauci-immune

HELLP syndrome

Drug-induced; e.g., PTU, methimazole

6-3

6-4

LABS

Know:

MAJOR HISTOCOMPATIBILITY COMP LEX:

•

C2 or C4--usually a genetic allele deficiency.

HUMANLEUKOCYTEANTIGENS

•

C3 is consumed with any activation of the complement

Overview

pathway (classical or alternative). •

C4 is consumed only with activation of the classical pathway (as with SLE).

•

CH50 assay measures total hemolytic complement

There are 2 main classes of major histocompatibility complex (MHC) human leukocyte antigens (HLA) antigens: •

Class I includes the HLA-A, HLA-8, and HLA-C

of the classical pathway and requires all components

antigens, which interact with CD8 or T suppressor

(C1-C9) of the classical pathway for a normal result.

cells. •

The CH50 assay is most useful as a screening tool for

Class II includes the HLA-D antigens; e.g., DR2, DR3, and DR4, which interact with CD4 or T helper

disease states resulting in hypocomplementemia. A low CH50 should prompt you to order the individual complements listed above to help you in your diagnosis.

cells. •

between MHC and CD T cells is that both form a

For example, patients with recurrent or severe neisserial

product of 8-MHCI x CD8= 8, while MHCII x

(meningococcal or gonococcal) infections may have terminal

complement

deficiency

(C5-C9).

CD4= 8.

Patients

with SLE may have low C3 and C4; C3 is a more sensitive index of disease activity in SLE. Therefore, normalization of individual complement levels and CH50 can be used to follow disease activity.

Note: An easy way to remember this relationship

HLA-827 Know when HLA-827 is found: •

Reactive arthritis: 60-80%, higher when sacroiliitis

•

Ankylosing spondylitis (AS): 90%.

•

Psoriatic arthritis: up to 60% (particularly with

is present.

RHEUMATOID FACTOR AND ANTI-CCP Rheumatoid factor

(RF)

is an auto-antibody that binds

spinal/axial disease).

to the Fe region of IgG. It is positive in 80-85% of patients with RA, which makes

a fairly sensitive

•

Inflammatory bowel disease (IBD) with associated axial joint arthritis: up to 60%.

test for RA, but it is not specific because a positive

But there is no HLA-827 association when only

RF can be seen in other diseases, including: chronic

appendicular joint disease is present in IBD patients.

lung disease, chronic infections (e.g., TB, HIV, viral hepatitis), Sjogren's, SLE, infectious endocarditis, and

Note that if axial disease is present, HLA-B27 is

hematologic malignancies.

typically positive. Keep in mind that 7-8% of the healthy

The anti-citrullinated cyclic peptide (anti-CCP antibody), however, is highly specific for RA (specificity

�

97%)

and tends to portend a poorer prognosis. The presence of both RF and anti-CCP antibodies is associated with more aggressive RA and extra-articular manifestations (e.g., rheumatoid nodule, rheumatoid lung/interstitial lung disease).

Caucasian

North American

population

carries

this

haplotype; therefore, an individual with HLA-B27 has only a I 0-20% risk of developing an HLA-827-related disease. Consequently, this test has limited clinical usefulness if not ordered in the right clinical scenario. A negative HLA-B27 test is useful in ruling out ankylosing spondylitis. See Table 6-3.

HLA-DR2, 3, 4 Table 6-3: lnc1dence of HLA-827

DR2 is

Ankylosing spondylitis

90%

Reactive arthritis; typically secondary to

60-80%

DR3

are found

associated in

with

Sjogren

SLE.

DR3

syndrome

and

polymyositis. DR4 antigens are associated with severe

GU/GI infections

RA. More in Allergy & Immunology, Book 4. Other important general HLA associations to know:

-----

and

occasionally

jejuni and C. trachomatis arthropathy

50%

1) HLA-85701 is strongly associated with abacavir hypersensitivity reaction (see Infectious Disease,

50% Healthy Caucasian population

7-8%

Rheumatoid arthritis, osteoarthritis,

10%

rubella arthritis

Book

1).

HLA-851 is associated with Beh«;:et disease.

3) HLA-DQ2/DQ8 is associated with celiac disease (see Gastroenterology, Book 1 ).

Although it does not cause reactive arthritis,

Klebsiella pneumoniae has

an enzyme (not encoded)

that cross-reacts with the HLA-B27 test.

THE JOINT

THE JOINT S YNO VIAL FLUID AND CRYSTAL •

ANALYSI S

Name 2 diseases that consume complement during a flare.

•

Synovium and synovial fluid: Type A cells of the

Other than rheumatoid arthritis, a positive RF can

synovial membrane are phagocytic, whereas type B

be seen with what other diseases?

cells probably synthesize hyaluronic acid. Chondrocytes

What antibody test is more specific than RF for

make the cartilage. Cartilage is avascular and depends on the synovial fluid for nutrients. The chondrocytes

rheumatoid arthritis? •

Compare and contrast "normal," "noninflammatory," "inflammatory," and "septic" joint fluid.

response (WBC/mm3). The WBC count in aspirated joint

Describe gout crystals and their birefringence.

fluid decreases rapidly, so analyze it immediately. See Table 6-4.

ERYTHROCYTE SEDIMENTATION RATE

Also, know that frank blood (hemorrhagic joint) can be

AND C-RE ACTIVE PROTEIN The

erythrocyte

sedimentation

slight damage is repairable. Joint fluid is categorized based on the inflammatory

(See Table 6-4.) •

can produce only a limited amount of collagen, so only

caused by trauma, bleeding diathesis, tumor, and pig rate

(ESR)

and

C-reactive protein (CRP) are the most common acute phase reactants (APRs; inflammatory markers) used in clinical medicine. They are most helpful in determining disease activity and response to therapy.

mented villonodular synovitis (PVNS). Look for crystals in inflammatory fluid using the polarizing microscope. Look for monosodium urate crystals (gout) and calcium pyrophosphate dihydrate (CPPD) crystals (pseudogout). Both types have 2 colors: blue and yellow;

Unfortunately, they are of limited diagnostic utility.

hence, they are termed "birefringent." The crystals are

Although they are sensitive markers of inflammation

identified, however, by the color of the crystals that are

in general, they are not specific for any particular

parallel to the microscope's color compensator. (Crystals

disease. Diagnostically, they are most helpful in ruling

perpendicular to the color compensator are the opposite

out inflammatory disease, especially when the pretest

color.) Be concerned only about the crystal color that is

likelihood is low to moderate. Note that an extreme

parallel! If the crystals are yellow when parallel to the

elevation of the ESR (> I 00 mm/hr) is almost always a

compensator, they are termed "negatively birefringent,"

hallmark of serious underlying disease, most commonly

and when they are blue, they are "positively birefringent."

malignancy, infection, or vasculitis.

Uric acid (gout) crystals are yellow when parallel to the compensator (negatively birefringent), and they are needle-like. (Helpful hint: The double Ls in "yellow" are parallel to each other.) Table 6-4: Synov1al Flu1d Analys1s

Joint Fluid Normal

Other Findings

WBC (cells/mm3) (}-200

None RBC

Noninflammatory

200-2,000

Disease Associations Internal derangement

None

OA, trauma, neuropathic joints, hypertro

RBC

phic arthropathy, TB, PVNS; occasionally SLE, scleroderma, and rheumatic fever.

Inflam�atory

2,00(}-50,000

None

Intracellular, strongly negatively birefringent crystals (yellow)

RA, gout, pseudogout, SLE, scleroderma, reactive arthritis,' 'ankylosing spondylitis, TB or fungal infection

lntraceullar, weakly positively birefringent crystals (blue) RBC Septic

50,000-100,000

None

Septic joint (but gonococcal septic joint

Organisms on Gram stain

can be 10,000 cells/rnm3) RA (very inflarnmed), gout, pseudogout

6-5

6-6

GENETIC COLLAGEN DISORDERS

The following are the ones to remember. Marfan syndrome: •

Long limbs (outstretched arm length> height)

•

Pectus excavatum (sternum dips inward), or pectus

•

Aortic aneurysm/dissection

carinatum (sternum protrudes outward)

•

Ectopia lentis (lenses displaced upward) Heart valve disease

Ehlers-Danlos syndrome: variable skin hyperelasticity

and joint hypermobility. Several classifications: •

Classic type (old Types I and II)

includes most

severe form (easily scarred skin and hypermobile

Image 6-1: Birefringent crystals

joints)

CPPD (pseudogout) crystals are blue (weakly positive birefringent) when parallel to the compensator; they

•

CPPD crystals attract neutrophils and can cause a

you must see intracellular crystals, which are crystals within the neutrophils, as opposed to crystals just floating around freely in the joint space. Important: Crystalline and infectious arthritis can coexist, so it is important to always send studies for both. Again, you cannot simply look at a photo of a crystal and see whether it is positively or negatively birefringent; you must know the direction of the compensator dial. For instance, in Image 6-1, you see needle-shaped crystals (so probably uric acid), but you won't know

manifestations

Vascular type (old Type IV )

manifestations

predominantly skin, not joint, and predilection for

purulent joint similar to gout with high synovial fluid actually causing the inflammatory reaction in the joint,

predominantly joint, not skin

appear as small, rhomboid structures.

WBC count. To be very certain that the crystals are

Hypermobility type (old Type III)

rupture of large vessels •

Several other rarer types

Osteogenesis imperfecta (OJ): Defects in procollagen

genes cause the variants, but all have: •

Osteopenia

•

Multiple bone fractures

•

Varying degrees of blue sclera

•

Lucent (brittle) teeth Hearing loss

There are 7 types of OJ; Type I is autosomal dominant and the mildest.

they are negatively birefringent unless the compensator

Pseudoxanthoma elasticum: autosomal recessive and

is vertical and the vertical crystals are yellow (yellow

involves skin (easy bruising), blood vessels, and eyes. The

parallel

�

gout).

main problem is recurrent UGI bleeds as they affect the elastic media of blood vessels. Classic findings include a cobblestone appearance of the skin with yellow papules

IMAGING STUDIES Weight-bearing knee films are the initial diagnostic tests of choice for nontraumatic knee disorders (RA or OA) because weight bearing allows a more realistic

and plaques that resemble "plucked chicken skin" on the neck/axillae and angioid streaks on funduscopic exam. (But this also occurs in Paget disease!)

evaluation of the joint space. If necessary, MRI can visualize

all

the

components,

except

for

normal

RHEUMATOID A RTHRITIS

synovium (too thin).

OVERVIEW The

GENETIC COLLAGEN DISORDERS The inherited disorders of collagen encompass several different diseases, many of which cause hypermobility e.g., Marfan syndrome, Ehlers-Danlos syndrome (EDS), and homocystinuria. Defects in elastic fiber formation (Marfan syndrome) or in type II collagen (Stickler syndrome) are well defined; responsible for these syndromes.

worldwide

prevalence

0.5-1%.

Women outnumber men 3: 1. The typical age of onset

different proteins are

is 40--50 years. Etiology of RA is multifactorial and basically unknown. There is a low concordant incidence of RA in identical twins, but RA does seem to have some genetic basis (

10% of patients have a 1" degree relative

with RA; higher concordance in identical twins than in fraternal ones). It is now recognized that RA is a heterogeneous disease with various HLA polymorphisms resulting in anything from

mild joint

involvement

severely

erosive

RHEUMATOID ARTHRITIS

They include: •

interleukins(especially IL- l , IL-6, and

•

B cells forming antibodies(RF and anti-CCP),

•

colony-stimulating factors(CSF),

IL-17interferons), •

Describe pseudogout crystals and their birefringence.

•

Which factors suggest aggressive RA?

•

growth factors, and

•

tumor necrosis factor (TNF-a; also important when

How long is the typical morning stiffness in RA?

considering treatment for RA).

lnOA? •

SIGNS I SYMPTOMS OF RA

What are the essential diagnostic criteria for RA?

Signs and symptoms of RA include > I hour of morning joint deformity. These genetic haplotypes have been

stiffness/pain

identified, and tests are commercially available to help

low-grade fever, anorexia, and weight loss. Remember:

predict which patients will develop aggressive disease and benefit from early pharmacotherapy.

that

improves

with

activity,

fatigue,

Noninflammatory joint diseases, such as OA, cause < 30 minutes of stiffness, and pain is worse with activity.

As mentioned under Labs, rheumatoid factor (RF) is positive in only 80-85% of patients with RA. It may take up to 2 years for patients with RA to become

Buzzwords is

for

symmetric

both and

RA and

polyarticular.

SLE:

The

There

arthritis specific

involvement of the hands-especially the MCP and

RF positive.

PIP joints (Image 6-2); the DIP joints are spared!

Know that anti-CCP antibody:

Boutonniere

and

swan-neck

deformities

occur

advanced disease, although they are nonspecific for RA.

•

appears earlier than RF,

•

has greater specificity for the diagnosis of RA(97%),

•

is associated with more aggressive disease and

and

Symptoms of RA may be intermittent (15-30%) or progressive. Intermittent disease has remissions lasting up to 1 year and is considered a variant of RA known as palindromic rheumatism.

extraarticular involvement. Antibodies play a prominent role in the current 20I 0 ACRIEULAR diagnostic criteria for RA. A high titer of either RF or anti-CCP contributes 3 of the 6 points required for the diagnosis.

Know the diagnostic criteria for RA, which changed in 2010. A complete list of criteria can be found in the 2010 ACRIEULAR guidelines on the American College of Rheumatology website at www.rheumatology.org. From this, remember the following essentials-RA can

Poor prognostic indicators of RA include: •

presence of HLA-DR4 antigen(HLA-DRB I *040 I),

•

high-titer RF or anti-CCP antibodies,

•

elevated acute phase reactants(ESR and CRP),

•

multiple joint involvement(> 6),

•

constitutional symptoms,

•

radiographic evidence of erosive disease, and

•

extraarticular disease(e.g., rheumatoid nodules,

be diagnosed when all of the following are present: •

Inflammatory arthritis(from 1 to

•

RF and/or anti-CCP

•

Increased ESR or CRP

•

Duration > 6 weeks

I 0 joints)

Other causes must be excluded (especially if symptoms have been present for< 6 weeks), such as SLE, Sjogren's, overlap syndromes, sarcoidosis, and viral reactive arthritis

vasculitis, lung involvement).

(i.e., hepatitis B and C, parvovirus B 19).

In an affected RA joint, there is inflamed synovium(with increased type A and B synovial cells). In its chronic phase, this inflamed membrane of granulation tissue (pannus) stimulates the release of cytokines, which leads to cartilage destruction, bone erosion, and an inflammatory synovial fluid that has decreased viscosity. Present in the synovium of the rheumatoid joint are cytokines and chemokines,

which are

secreted

activated lymphocytes, macrophages, and fibroblasts; these probably account for most of the destructive effects of RA.

Image 6-2: Rheumatoid arthritis ofthe metacarpophalangealjoints, with an endarteritis-associated ulcer on dorsum

6-7

6-8

RHEUMATOID ARTHRITIS

Seronegative RA is diagnosed when patients meet other criteria but lack both RF and anti-CCP. These patients tend to have less severe disease than what is seen in antibody-positive patients. Hemochromatosis is another disease that commonly involves the 2"d and 3'd MCP and PIP joints, but the arthropathy of hemochromatosis is distinctly asymmetric. Also, hemochromatosis has hook-like osteophytes on the MCP joints and chondrocalcinosis neither finding is seen in RA. Patients can easily be screened for hemochromatosis with iron studies. An elevated transferrin saturation (Fe/TIBC of> 45%) or elevated ferritin level suggests the diagnosis. Know these clues for differentiating RA and SLE from hemochromatosis. Hoarseness, sore throat, and/or neck pain may indicate involvement of the cricoarytenoid joint in the patient with RA. The temporomandibular joints may also be affected. The knee is the most common single joint initially involved in RA; but, over time, small joints-in a symmetric fashion-are more commonly involved. In fact, the forefoot has proven to be the site of earliest radiographic changes in RA, and the head of the 51h metatarsal bone may be the location of the earliest erosion. Carpal tunnel and tarsal tunnel syndromes can occur in RA. If a patient with inflammatory knee arthritis presents with a swollen calf, suspect a ruptured Baker cyst (popliteal cyst) causing pseudophlebitis. Occasionally, a Baker cyst can cause extrinsic venous compression that can simulate a deep vein thrombosis. C-spine: Patients with chronic, severe disease may develop cervical instability at the atlanto-axial articulation (C l-C2). The rest of the axial skeleton is spared. While patients can be asymptomatic, suspect cervical (C l C2) involvement when a patient with RA complains of: •

•

recurrent occipital headaches, limited neck range of motion, or paresthesias of the hands and feet.

lumbar spine pain. If you see a patient withRA and spine pain, think about the myriad other potential causes of spine pain; e.g., compression fractures, infections-not a flare ofRA. EXTRAAR TICULAR MANIFESTATIONS

Remember: Extraarticular manifestations of RA are more common in the presence of RF and anti-CCP antibodies (seropositiveRA). Know these extraarticular manifestations ofRA: Cardiac: •

•

Renal (all very rare): •

•

Drug-related renal disease Amyloid renal disease occurring late inRA

Lungs (males more often): •

•

Exudative pleural effusion with low glucose (< 30 mg/dL) and pH. Diffuse interstitial fibrosis and intrapulmonary rheumatoid nodules; when caused by mine dust, it is called Caplan syndrome (mine dust pneumoconiosis).

Vasculitis: •

•

May resemble polyarteritis nodosa and cause nailfold infarcts and splinter hemorrhages. Necrosis with ulceration may occur, especially over the malleoli.

Nerves: •

•

If these symptoms are present, order cervical spine x-rays with flexion and extension views. InRA patients scheduled to undergo endotracheal intubation, an evaluation for cervical instability is mandatory. Acute subluxation, which may occur with extension of the neck for intubation, can cause spinal cord compression or vertebral artery compression leading to quadriparesis or sudden death.Remember: All patients with long-standing RA should have flexion and extension neck films before surgery to assess for subluxation.

Pericarditis (with effusion or thickening) and myocarditis. Rheumatoid nodules on the valves. Atherosclerosis-3x increased risk of atherosclerotic cardiovascular disease (sudden death and MI). Coronary artery disease is the leading cause of death among patients with RA.

Mononeuritis multiplex, which may manifest as foot or wrist drop Carpal and tarsal tunnel syndromes Cervical myelopathy

Eyes: •

•

Episcleritis Scleritis Sicca/secondary Sjogren syndrome

Skin: •

Rheumatoid nodules occur in 25% and indicate potential for more severe disease. These nodules usually appear on extensor surfaces but may also be found in the lungs and on heart valves.

The thoracic, lumbar, and sacral spine and the Sljoints are usually spared inRA (in contrast to ankylosing spondylitis and psoriatic arthritis). Again, RA does not present as

RHEUMATOID ARTHRITIS

Trials have shown that 70% of patients with active, polyarticular, RF-positive disease develop joint damage or erosions within 2 years of onset. Other trials show that early treatment with a DMARD may alter the course of the disease. Trials with combination DMARDs in

•

What is the pattern of arthritis in RA?

•

Which part of the spine is sometimes involved

early disease also show benefit. NSA!Ds may help with inflammation and pain, but do not prevent the formation

in RA? Which parts are never involved? •

•

of either erosions or joint deformities. Glucocorticoids,

What is the most common manifestation of RA

like DMARDs, can alter the course of disease but are

in the lungs?

associated with significant long-term side effects.

What is Felty syndrome?

Current treatment paradigms focus on early diagnosis

Name some indicators of active RA. If a patient

and early aggressive therapy to allow patients a chance at remission. The goal is to try to initiate DMARD therapy

has these indicators, when do you start treatment?

within 3 months of symptoms and, if needed, to titrate

With what?

drugs (add additional DMARDs or biologic agents) to attain low disease activity or remission. Previously,

Blood and lymphatics:

treatment of RA followed a pyramid regimen consisting

•

Anemia of chronic disease

initially of NSAlDs and glucocorticoids�with DMARDs

•

Neutropenia (seen in Felty syndrome and large

added only as the disease progressed. Now we know

granular lymphocyte [LGL] syndrome)

that RA-associated disability can be drastically reduced

Increased risk of lymphoma (particularly in

when treated early and aggressively.

•

longstanding, untreated, active disease) Felty

syndrome

consists

the

Recognize

classic

triad

that

glucocorticoid

controversial�influenced

the

use

efficacy

RA of

the

(the

spleen

biologics and the well-known side effects of systemic

These

patients

glucocorticoids. Generally, as the patient improves on

usually have long-standing disease associated with

early aggressive therapy, the more toxic drugs, such

high titers of rheumatoid factor and subcutaneous

as steroids, are withdrawn, while DMARDs and/or

rheumatoid nodules and suffer increased mortality from

biologics are used as maintenance therapy.

infections. Treatment: methotrexate, cyclosporine A,

Now we'll discuss these RA medications in more detail.

rheumatoid can

arthritis,

"felt-y"),

and

splenomegaly neutropenia.

corticosteroids, granulocyte colony-stimulating factor (GCSF), and, if needed, splenectomy. If splenectomy is ineffective, the prognosis is poor. TNF inhibitors are currently being evaluated. Large

granular

lymphocyte (LGL)

syndrome

may

be difficult to distinguish from Felty syndrome since it

also

presents

with

neutropenia,

Table 6-5: Drugs Used to Treat RA

splenomegaly,

and susceptibility to infections. It differs from Felty

Nonsteroidal

Nonselective (e.g., ibuprofen,

syndrome in that it is less commonly associated with

naprosyn, nonacetylated

RA and rarely may progress to LGL leukemia. In

salicylates) and COX-2 inhibitor

contrast to Felty syndrome, these patients do poorly with splenectomy. Definitive diagnosis can be made by detecting clonal T-cell gene rearrangement, which is not present in Felty syndrome.

Nonbiologic

Methotrexate, leflunmide,

DMARDs

hydroxychloroquine, sulfasalasine

Immunosuppressants

Azathioprine, chlorambucil, corticosteroids, cyclophosphamide, cyclosporine, mycophenolate

TREATMENT OF RH EUMATOID ARTHRITIS

mofetil, tacrolimus

Overview Drugs used to treat RA (see Table 6-5) are categorized as

Biologics

antibodies and soluble receptors),

nonsteroidal antiinflammatory drugs (NSAIDs), which

IL-l and IL-6 antagonists,

help with pain but do not modify the disease course: •

anti-B cell antibody, T-cell inhibitor

Nonbiologic disease-modifying antirheumatic drugs (DMARDs)

TNF inhibitors (monoclonal

Miscellaneous

Acetaminophen, colchicine,

•

Immunosuppressants

•

Biologics or biologic response modifiers (BRMs)

plasma exchange, thalidomide,

•

Miscellaneous (steroids, minocycline, doxycycline)

intraarticular viscosupplementation

dapsone, IVIG, plasmapheresis/

6-9

6-10

RHEUMATOID ARTHRITIS

NSAIDs

DMARDs

NSAIDs are part of the initial treatment. NSAIDs

General Characteristics

decrease inflammation and joint swelling but do not alter the course of the disease. Again, know that DMARDs (next) are now given with onset of RA symptoms. NSAIDs are added to help control pain.

Disease-modifYing antirheumatic drugs (DMARDs): •

Methotrexate (MTX)

•

L eflunomide (LEF)

•

Hydroxychloroquine (HCQ)

or choline salicylate. These nonacetylated salicylates do

•

Sulfasalazine (SSZ)

not cause an ASA allergy reaction and also may have

•

Azathioprine (AZA)

•

Cyclosporine A (Cyc A)

•

Cyclophosphamide (Cytoxan®)

For patients with ASA allergy, use a sodium, magnesium,

less GI toxicity (but may be less effective). What COX-2

about

the

inhibitors,

COX-2 like

inhibitors?

other

Selective

NSAIDs,

inhibit

cyclooxygenase-2 but, unlike other NSAIDs, do not inhibit cyclooxygenase-1. Currently, the only COX-2 inhibitor available in the U.S. is celecoxib (Celebrex®), which is approved for treatment of RA, OA, ankylosing spondylitis, and acute pain (and adjunctive for familial

DMARDs are a major component of RA treatment.

G R

They have a slow onset of action (several months), so concurrent NSAIDs or low-dose glucocorticoids are required initially. HCQ and SSZ are sometimes used first in cases of early, mild RA; these drugs are also safe in pregnancy and breastfeeding. DMARDs are

V d ti e

started with onset of symptoms. Aggressive treatment

adenomatous polyposis).

with MTX, LEF, SSZ or combination DMARDs is

The antiinflammatory effects of COX-2 inhibitors are

recommended

comparable to other NSAIDs, with possibly reduced GI

disease. The following DMARDs are recommended by

patients

with

moderate-to-severe

the 2012 American College of Rheumatology updated

irritation and ulcer development. Other benefits of selective COX-2 inhibitors: no effect on platelet function, so bleeding time is unchanged; less than other NSAIDs to precipitate bronchoconstriction in patients with aspirin-induced asthma.

The problem with selective COX-2 inhibitors (and

adverse cardiac events such as myocardial infarction,

stroke, heart failure, and sudden cardiac death in some patient groups. Celecoxib is contraindicated in patients who are in the postoperative recovery phase after

r i h

Methotrexate

MTX is an antifolate agent with

antiinflammatory

properties that is very effective in the treatment of

NSAIDS in general) is that they increase the risk for

9 9

clinical practice guidelines.

n U

risk of bleeding in anticoagulated patients; less likely

artery bypass graft. One trial of 4,000 patients showed celecoxib increased risk of death or recurrent MI

( 2x) �

if taken longer than I month after an MI. Analysis of 2 recent long-term adenoma prevention trials studying celecoxib concluded there is an increased risk of serious

for

cardiovascular events that may be dose-dependent. Patients who are allergic to sulfa appear to have a high risk of rash with COX-2 inhibitors.

RA. Because it has the most predictable benefit and is

usually the best tolerated, the 2012 American College

of Rheumatology updated clinical practice guidelines

recommend MTX as the initial DMARD for patients with moderate-to-severe RA without poor prognostic

features and as the main DMARD when combination therapy is used in those with poor prognostic features. Again, most experts are now starting DMARDs with onset of RA symptoms! Some patients begin to improve within 6 weeks. It is administered orally, subcutaneously, or intramuscularly I x/week and is often combined with other agents to maximize disease control. Preexisting liver disease (e.g., HBV, HCV, heavy alcohol use), severe renal disease, and pregnancy are contraindications to using this drug.

Know these important drug interactions: NSAIDs and lithium have common excretory pathways, so check

Common side effects

and complications of

MTX

include:

lithium levels periodically if a patient is receiving both

•

Alopecia

meds. ASA decreases the breakdown of oral hypoglyce

•

GI distress (nausea, vomiting, diarrhea, mucositis)

•

Bone marrow suppression even at low doses

mics, so decrease dosage of these when given with ASA. All NSAIDs, selective and nonselective, may precipitate

(Prescribe folate replacement 1 mg/day for

or worsen heart failure and may raise blood pressure.

prevention. Coadministration of sulfa drugs or antifolate agents can worsen cytopenias, so follow CBC.) •

Increased liver transaminases (AST/ALT)

RHEUMATOID ARTHRITIS

Important:

Because

LEF

has

extremely

long

half-life and is teratogenic, women planning to conceive

Q�uiz

must discontinue the drug and undergo treatment with cholestyramine to eliminate the drug.

Which DMARDs are used to treat mild RA and

•

are relatively safe during pregnancy?

Hydroxychloroquine

Which DMARD is recommended by the American

•

The main side effect to know is retinopathy. The usual

College of Rheumatology as 1st line for all

risk is considered to be 115,000 patients after prolonged

moderate-to-severe cases of RA?

use. If renal dysfunction occurs, the risk of retinopathy rises greatly. Patients started on HCQ need a baseline

What are methotrexate contraindications?

•

ophthalmologic evaluation to serve as a reference point

Name another DMARD recommended to treat RA

•

and to rule out existing retinopathy. After 5 years of

in patients who cannot tolerate methotrexate.

continuous HCQ, annual exams are recommended in

What follow-up is required in patients treated with

•

G R

average-risk patients. Routine CBC and CMP should be

hydroxychloroquine?

obtained every 3-6 months. Also, consider monitoring muscle strength periodically because of the risk of

Other serious, but less common, reactions to be aware

myopathy. Know that the use of HCQ in psoriatic

of include:

patients may exacerbate psoriasis.

•

increased susceptibility to opportunistic infections, nephrotoxicity (follow creatinine), and

Also

MTX

pneumonitis

used for inflammatory bowel

In RA,

pneumonitis/pulmonary fibrosis.

The

V d ti e n U Sulfasalazine

severe hepatotoxicity (follow AST/ALT),

idiosyncratic

(i.e.,

non-dose-related). Initial symptom is nonproductive cough. Radiograph is initially normal but shows alveolar infiltrates in later stages.

the sulfapyridine portion of

disease (IBD). the molecule

produces effects; in IBD, the 5-amino salicylic acid

(5-ASA)

portion

the

effective

component. The

most common side effects are sulfa-allergic reactions, nausea, vomiting,

diarrhea, and crampy abdominal

pain. It may cause reversible oligospermia (no effect on

MTX-related toxicities are not age-related. Monitor CMP and CBC every 4 weeks for the first 3 months

of therapy, then every 12 weeks thereafter; labs should be monitored more frequently if clinically indicated.

9 ri 9

Baseline hepatitis B and C serologies and CXR should be obtained prior to initiating therapy. Order pulmonary

function tests in patients with symptoms of dyspnea or a

female reproduction), cytopenias, and an elevation in transaminases (monitor with periodic CBC and LFTs).

The 5-ASA component can cause Reye syndrome in

patients vaccinated with the varicella vaccine (because it's a live virus vaccine). Check G6PD levels in patients at increased risk for G6PD deficiency (e.g., males of

African or Mediterranean descent).

history of COPD (pay attention to the carbon monoxide

diffusing capacity [DLCO]). Monitoring renal function is

important

because

most

h ta

MTX

excreted

DMARDs in Pregnancy

unchanged in the urine. Renal failure from any cause

Essentially any DMARD or antirheumatic drug taken

leads to accumulation of the drug and increased toxicity.

during pregnancy, especially during the 1" trimester

Leflunomide

where organogenesis is predominant, can pose a risk to the fetus. The general rule is to avoid any and all drugs if at all possible. If a medication is required, the minimal

LEF (Arava®) is used to treat RA. It is a pyrimidine

effective dose to maintain the disease under control is

antagonist and may be used as an initial DMARD in

recommended.

patients unable to take MTX.

The following are general recommendations:

Its side effects are very similar to MTX. Minor adverse reactions include diarrhea and respiratory infections.

•

during pregnancy.

Its major side effect is hepatotoxicity, and it should be avoided in those with preexisting liver disease.

•

interstitial

lung

disease,

Screen for latent TB before prescribing this drug. CBC, LFTs, and creatinine need to be monitored frequently, as with MTX. The drug is contraindicated in pregnancy and unsafe for lactation.

MedStudy

(weigh risks vs. benefit).

peripheral

neuropathy, and opportunistic infections.

Azathioprine, IVIG, cyclosporine A, and cyclophosphamide are relatively contraindicated

Other important side effects include cytopenias, renal dysfunction,

Hydroxychloroquine and sulfasalazine are allowed

•

Methotrexate, leftunomide, and mycophenolate mofetil are absolute contraindications.

6-11

6-12

RHEUMATOID ARTHRITIS

Biologic Agents

Anti-TNF Biologics (TNF Inhibitors)

See Table 6-6 for a synopsis of the biologics currently

Infliximab, adalimumab, certolizumab, and golimumab

approved for RA. Biologics are made with animal,

are monoclonal antibodies that bind and inactivate

microbial, or human proteins, in contrast to DMARDs,

tumor necrosis factor (TNF), an important mediator

which are made from chemicals. The biologics have opened a new era in RA treatment in that they are

of the inflammatory response in RA. Etanercept is a

highly selective in their targets, yielding better efficacy

binds and inactivates TNF. It has been suggested that

soluble TNF receptor that is linked to IgG 1 and also

with improved safety profiles. They are designed to

monoclonal anti-TNF agents may cause greater risk for

inhibit specific components of the immune system

infections (e.g., TB, herpes zoster, nonserious infections

that

[NSIEs]) compared to etanercept. The anti-TNF drugs are approved for a variety of indications, including RA,

regulate

inflammation.

They

can

broken

down into those that inhibit tumor necrosis factor (anti-TNFs) or those that inactivate other pivotal sites

psoriasis, psoriatic arthritis, ankylosing spondylitis, and

related to inflammation.

inflammatory bowel disease.

G R V

Table 6-6: Biologics Drug Name

Approved Use

Brand Name

TNF-a inhibitors

Most Common Side Effects Boxed warnings: Serious infections and TB

Infliximab

Remicade®

RA, P,AS, Crohn 's, UC

d e

URI, nausea,headache,infusion reactions, DIL with antinuclear and anti-dsDNA ab

Adalimumab

Humira®

RA, P,AS, Crohn's

Certolizumab

Cimzia®

RA, Crohn's

t i n

URI,headache, rash

URI, headache, nausea

URI

Etanercept

Non-TNF-a inhibitors IL-l antagonist Anakinra

Rituximab

h a

Tocilizumab

Anti-CD20

9 9

Kineret®

IL-6 antagonist

Rituxan®

U -

RA,P,AS

EnbreJ®

Refractory RA

URI, headache, rash, local site reaction,DIL with

antinuclear and anti-dsDNA ab

Boxed warning: Serious infections, do not combine with TNFi Neutropenia, headache, local site reaction

Boxed warning: Serious infections and TB URI, increased LFTs, neutropenia, serious GI infections

RA(with MTX)

Boxed warning: Fatal infusion reactions,

anti-CD20+ NHL

progressive multifocal leukoencephalopathy,

anti-CD20+ CLL

severe mucocutaneous reactions

GPA

Fever, nausea/diarrhea, cytopenias, peripheral edema, hypertension or hypotension, rash;·

MFA

headache, neuropathy T-cell inhibitor Abatacept

Orencia®

Refractory RA

Boxed warning: COPD exacerbation, avoid combining with TNFi Infections, headache

RA = rheumatoid arthritis; P = psoriasis/psoriatic arthritis; AS = ankylosing spondylitis; UC = ulcerative colitis; NHL = non Hodgkin lymphoma; CLL = chronic lymphocytic leukemia; MTX = methotrexate; GPA= granulomatosis with polyangiitis; MPA= microscopic polyangiitis

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

RHEUMATOID ARTHRITIS

These potential complications sound terrible (and they are!), but know that they are not common-the most common side effect is an increase in NSIEs as upper respiratory tract infections and urinary tract infections. •

What are the categories of biologics used

Patients with active infections that have potential to

to treat RA? •

•

progress to serious infections need to discontinue their

What are representative drugs for each category

biologic or delay treatment until the infection has

of biologics?

resolved. Less common but noteworthy complications include worsening psoriasis and reactivation of HBV.

Name some serious complications of the

[Know:] Because DMARDs and biologics can suppress

various biologics. •

the immune system and increase susceptibility to infec

What is the most common side effect

tion, routine vaccinations for influenza and pneumonia

of the non-TNF biologics?

are recommended; patients on biologics,

[Know:] For RA, these agents are most beneficial when combined with methotrexate and have been shown to halt and possibly heal erosive damage! lupus as well as other side effects including: injection site/infusion reactions, infections, increased risk for cancer,

cytopenias,

CNS

demyelination,

and

worsening heart failure. They are not recommended for patients with NYHA class III/IV heart failure and an ejection fraction :5 50% because they may worsen CHF symptoms and increase morbidity. Inftiximab has been associated with fatal hepatosplenic T-cell lymphoma.

IL-l; tocilizumab

inhibitor combination. Anakinra is associated with a

9 ri 9

high percentage of injection site reactions. Leukopenia, and

hyperlipidemia

associated with tocilizumab.

have

been

Rituximab is an anti-CD20 antibody directed against B

cells, which are believed to mediate progression of RA. It

h ta

is used in combination with MTX to treat RA in patients refractory to TNF inhibitors. Stevens-Johnson syndrome, and

epidermal deadly

necrolysis,

infusion

tumor

reactions

lysis

(e.g.,

syndrome,

hypotension,

bronchospasm, acute respiratory distress syndrome, Ml, progressive

AZA has shown some benefit for RA, but is much more

commonly used in SLE. Its main side effects include bone

marrow suppression, NN, diarrhea, and hepatotoxicity. It is important to understand AZA's metabolism. It is liver. AZA and 6-MP are inactive prodrugs. 6-MP can

IL-6) are used to treat RA refractory to the MTX/TNF

toxic

Azathioprine

then be metabolized by

Interleukin antagonists (anakinra

abnormalities,

V d ti e n U Immunosuppressants

first metabolized to 6-mercaptopurine (6-MP) by the

Non-TNF Biologics

LFT

G R

2012 guidelines. The only live vaccines that are relevant to clinical practice are MMR and shingles vaccines.

These agents have been associated with drug-induced

skin

prednisone

> 20 mg/day, methotrexate > 25 mg/week, and azathio prine > 3 mglkg/day should avoid live vaccines per ACIP

multifocal leukoencephalopathy

[PML])

have been described in patients receiving rituximab. In the last few years, there have been case reports of PML associated with rituximab. If there is a scenario where

3 different pathways.

Two important things to know:

I) Thiopurine methyl transferase (TPMT) is an enzyme in the main metabolic pathway for 6-MP. Patients with heterozygous or homozygous mutations in this

enzyme ( I 0% of population) are prone to severe AZA toxicity. Some experts recommend testing for this mutation because patients with this deficiency should be given lower doses of AZA. 2) Xanthine oxidase (XO) is an enzyme in another important metabolic pathway for 6-MP. This is important because allopurinol, a drug that inhibits XO, can lead to increased levels and toxicity of AZA. The recom mendation is to decrease the dose of AZA by at least half in the patient on allopurinol or febuxostat and to monitor CBC and LFTs closely.

an RA patient has new onset CNS symptoms after

Cyclosporine A

receiving rituximab, PML should be on the differential

In doses of 2.5-4 mglkg/day, it has been shown to have

diagnosis. Abatacept is a selective T-cell costimulation inhibitor used to treat refractory RA. Activated T cells are increased in the synovium of patients with this disease. Avoid live-virus

Cyclophosphamide vaccines

patients prescribed a

biologic, and screen all patients for tuberculosis.

synergistic effects when added to MTX, but its use has been limited by renal toxicity and hypertension.

In RA treatment, use is limited to treating RA-associated vasculitis.

6-13

6-14

SYSTEMIC LUPUS ERYTHEMATOSUS

Miscellaneous

SLE: Joints

Minocycline and Doxycycline

Lupus arthritis is inflammatory and nonerosive. Involved

These drugs are not FDA-approved for RA. They are occasionally beneficial as mild DMARDs for some RA patients because of their metalloproteinase inhibition, although they may be more effective in patients with spondyloarthropathies.

joints may be symmetrical, asymmetrical, oligoarticular, or polyarticular; the small joints of the hands and wrists and the knees often are affected (Image

6-3).

Jaccoud

deformities of SLE appear like boutonniere deformities ofRA, but with SLE, these deformities are easily reducible (looks like normal hands when you stretch out the joints; RA hands won't yield to pressure). Note that some SLE

Glucocorticoids

patients may have concomitant RA (lupus-RA overlap or

Low-dose oral prednisone(< 10 mg/d or equivalent) and

"rhupus"); in these cases, joints may have erosions.

joint injections of glucocorticoids are very effective for relieving symptoms ofRA. Joint injections have dramatic but temporary effects on symptoms but do not slow the systemic disease process. Low-dose oral glucocorticoids

SLE: Skin and Mucous Membranes

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All lupus rashes are photosensitive and can occur even

may decrease the rate of erosion; however, the side effects

when the weather is cloudy.

of glucocorticoids limit their use-weight gain, infec

Classification of lupus rashes:

tion, osteoporosis, easy bruising, adrenal insufficiency,

V d ti e n U

diabetes mellitus, peripheral edema, hypertension, insom

•

a.k.a. discoid lupus erythematosus

nia. Due to risk for RA flare and also adrenal insufficiency, glucocorticoids should be tapered slowly.

Chronic cutaneous lupus erythematosus

(CCLE), (OLE):

hyperpigmented edges, which may be raised,

frequently cause central scarring/atrophy with destruction of melanocytes and hair follicles. Many

patients with SLE also have discoid rashes, but

patients with discoid lupus have only a 5% chance

SYSTEMIC LUPUS ERYTHEMATOSUS

of developing SLE ( Image

MANIFESTATIONS OF SYSTEMIC LUPUS Overview

arthralgias,

disease. and

fatigue

ranges to

from

severe, SLE

primarily

h ta

Image 6-3: Symmetric polyarthritis ofSLE

(ACLE):

I mage

6-6), forehead,

upper chest, neck, ears, upper

extremities, and back that flares with systemic

affects

disease.

women of childbearing age; prognosis is worse in males, be affected.

Acute cutaneous lupus erythematosus

malar rash ("butterfly" that spares nasolabial fold;

rash,

African-Americans, and Hispanics. Any organ system can

6-5) and

erythematous, concentrated on sun exposed areas

life-threatening

9 ri 9

manifestations (renal/CNS).

mild

Image

significant renal manifestations.

•

Systemic lupus erythematosus (SLE) is the prototypic autoimmune

6-4 and

typically have a milder disease course devoid of

•

Subacute cutaneous lupus erythematosus

(SCLE):

annular rash. This rash can be seen with Sjogren's as well; patients can have negative ANAs with +RolLa. Certain medications may bring out this rash, includ ing calcium channel blockers. •

"Other": lots of other rashes (e.g., tumid lupus, chilblains lupus, urticaria, vesicles, lichen planus).

Image 6-4: Discoid lupus

Image 6-5: Discoid lupus

SYSTEMIC LUPUS ERYTHEMATOSUS

commonly associated with antiphospholipid abs). CAD is the most common cause of death in patients with SLE.

SLE: Kidney

•

Characterize the pattern of arthritis in SLE.

•

What are the patterns of skin rashes in SLE?

•

What is the most common cause of death in

is associated with glomerulonephritis and the nephrotic

patients with SLE?

syndrome.

•

Glomerulonephritis is a major cause of morbidity and mortality in SLE patients. The presence of anti-dsDNA

What is the increase in risk of myocardial infarctions

African-American lupus patients are more likely than

in women with SLE?

Caucasians to develop aggressive renal disease. Once

Which autoantibodies are associated with

lupus nephritis develops, lifetime recurrences are likely.

development of lupus nephritis?

"Bad"

What classifications of SLE kidney disease require

associated with an active urine sediment: proteinuria (usu

kidney

disease

(advanced

classifications)

G R

ally> 500 mg/day or nephrotic> 3.5 g) and microscopic

treatment with cytotoxics?

hematuria, as well as a high titer of anti-dsDNA. Always perform aU/A on any patient whom you suspect has SLE.

Alopecia is common; typically nonscarring. Aphthous (mucosal) ulcers are usually painless and can occur in the nasal passage as well as the oropharynx.

V d ti e n U

Kidney disease is staged by the International Society

of Nephrology (ISN) and the Renal Pathology Society (RPS)-this replaced the WHO classification system. These classifications organize renal disease according to

SLE:Lung

chronicity and activity level. Although the classification

Lung disease in lupus can manifest as pleuritic chest pain +/- effusion (most common), alveolar infiltrates, pneumonitis (with subsequent fibrosis and pulmonary arterial

hypertension),

and

alveolar

hemorrhage

a medical emergency that carries a 50% mortality rate!

SLE:Heart

The Framingham Offspring Study revealed that women

ages 35-44 with SLE have a 50-fold increase in myo

9 ri 9

cardial infarctions. The early CAD is thought to be due to chronic inflammation and steroid use, both of which accelerate atherosclerosis.

Other cardiac involvement found

SLE

patients

includes: pericarditis (most common), myocarditis, and

h ta

Libman-Sacks endocarditis (sterile fibro-fibrinous veg etations that can mimic infectious endocarditis and are

system focuses on glomerular disease, know that systemic

lupus also can affect the tubules and vasculature. ISN!RPS classification (treatment) of glomerulonephritis

in SLE: •

Class 1: minimal mesangial (no treatment needed)

•

Class II: mesangial proliferative (no treatment)

•

Class Ill: focal proliferative;:::; 50% of glomeruli

(steroids and cytotoxics)

•

Class IV: diffuse proliferative (steroids and

•

Class V: membranous (steroids, cytotoxics, and

cytotoxics)

ACE inhibitor or ARB to decrease proteinuria) •

Class VI: advanced sclerotic;� 90% sclerotic

glomeruli (disease irreversible) Combinations of the above stages may occur. The letters "A" and "C" are also listed as subcategories to reflect whether the changes are "active" or "chronic." Important: Treat class III and IV disease with cytotoxics and corticosteroids to prevent end-stage kidney disease, which develops within 2 years in untreated patients. Cytotoxics

typically

used

are

cyclophosphamide,

mycophenolate mofetil, or azathioprine. Note: Membranous nephropathy is often associated with nephrotic syndrome, and thrombophlebitis is a complication.

SLE: Blood Immune can

mediated

include:

cytopenias

leukopenia

are

common

and

(specifically lymphopenia),

thrombocytopenia, and hemolytic anemia. Note that Image 6-6: Malar rash of SLE

MedStudy

headache

thrombocytopenia

microangiopathic

6-15

6-16

SYSTEMIC LUPUS ERYTHEMATOSUS

hemolytic anemia + acute renal failure in a SLE patient suggests TTP-mortality is high if unrecognized and untreated! Plasmapheresis is indicated (more in Hematology, Book 4).

Know that patients with active SLE usually have low levels of C3 and C4. Current ANA testing uses a human cell line (HEp-2 cells) as the substrate and rarely pro duces a false-negative test. So, a negative ANA basically excludes SLE.

SLE: CNS (Neuropsychiatric Lupus)

In summary, in working up a case of possible SLE, first do an ANA. If negative, SLE is excluded. If the ANA is positive, continue on with an ANA profile.

Cognitive/behavioral changes (most common), headaches, psychosis, mood changes (e.g., depression), aseptic meningitis, organic brain syndrome, seizures, chorea, and strokes occur with SLE. Even severe abnor malities may clear rapidly with regression of disease. Spinal fluid may be normal, even with severe symptoms; but you may find elevated protein or WBCs (mostly lym phocytes), especially in patients with cerebritis. MRJ of the brain may show scattered areas of increased intensity, suggesting a vasculopathy. Evaluate all neuropsychiatric lupus patients for infection, including lumbar puncture, particularly if immunosup pressed. Know that anti-Smith, anti-neuronal, and antiribosomal P protein antibodies are associated with CNS disease.

The 1997 ACR classification criteria can be useful to establish a diagnosis of SLE. These criteria are designed to enroll a homogenous patient population into clinical trials, but can suggest SLE diagnosis in a patient with several signs/symptoms.

The following are the ACR diagnostic criteria in SLE, presented in the "SOAP BRAIN MD" mnemonic: •

•

9 ri 9

Serositis: pleuritis, pericarditis Oral ulcers: usually painless Arthritis: nonerosive Photosensitivity Blood disorders: low WBC, lymphs, hemolytic anemia Renal disease: proteinuria, RBC casts Antinuclear antibodies Immunologic phenomena (e.g., +anti-dsDNA; antiSmith [Sm] antibodies, anti-cardiolipin [ACL] abs) Neurologic disorder: seizure or psychosis Malar rash Discoid rash

h ta

Patients with SLE have a higher incidence of failed pregnancies. Pregnancy is not advised until disease has been quiescent for 6 months or longer. Risk of pregnancy complications (flares or fetal problems) is much greater if disease is active (especially renal manifestations) or if the mother has anti-dsDNA or antiphospholipid antibodies.

G R

V d ti e n U

DIAGNOSIS

•

SLE AND PREGNANCY

In fetuses/infants of mothers with SLE who have SSA (Ro) and SSB (La) antibodies, heart block can begin as early as the 2"d trimester (Table 6-1 on page 6-2). For these patients, begin serial fetal echocardiograms at about 16--18-weeks gestation. The risk for heart block and neonatal lupus is decreased with hydroxychloroquine. Favorable pregnancy outcomes are associated with quiescent disease, minimal medical therapy, and medi cations that can be continued during pregnancy (e.g., prednisone, hydroxychloroquine, and azathioprine).

Measure baseline complement levels, anti-dsDNA, SSNSSB, and a 24-hour urine protein before or very early in the pregnancy. Manage flares during pregnancy with glucocorticoids. Refer pregnant women with sys temic lupus to a high-risk obstetrician (and pediatric cardiologist, if appropriate).

The ANA is the most sensitive test for SLE (99% of patients with active disease have a positive test), but it has very poor specificity (can be positive in patients without the disease). Among the subtypes of ANA, anti-dsDNA and anti-Sm in high titers are very specific (usually negative in patients without disease; i.e., rarely false-positive), but they have low sensitivity (sometimes they are negative in patients with true disease). Never check anti-single-stranded DNA. It's a worthless test that is positive in many illnesses.

Women with antiphospholipid syndrome (APS) and a history of recurrent miscarriages can be treated with heparins (low-molecular-weight or unfractionated) plus low-dose aspirin to decrease the incidence of miscar riage. Patients with antiphospholipid antibodies are also at increased risk for HELLP syndrome (a variant of pre eclampsia with hemolysis, elevated liver enzymes, and low platelets).

Sometimes distinguishing a lupus flare with renal involvement from preeclampsia is difficult because both may present with increasing proteinuria, hypertension, lower extremity edema, deterioration in renal function, and thrombocytopenia. With lupus flares, SLE disease activity markers may be abnormal (high dsDNA Ab titer, low complements), serum uric acid is normal (< 5.5 mg/ dL), and urine sedimentation may be active (white cell casts, high number of red blood cells). These changes are not seen in patients with preeclampsia.

2014 MedStudy-Piease Report Copyright

Infringements to copyright@medstudy.com

SERONEGATIVE SPONDYLOARTHRITIS

Cytotoxics

(azathioprine,

or cyclophosphamide)

mycophenolate

are added

mofetil,

corticosteroids

for serious flares of SLE, particularly renal and CNS disease. Cyclophosphamide and corticosteroids improve •

•

What hematologic changes in SLE are among

survival in patients with SLE and class liT or IV

the criteria for diagnosis?

glomerulonephritis.

A pregnant woman with SLE has SSA (Ro) and

Anti-B-cell

SSB (La) antibodies. What abnormality can occur

are occasionally used in patients with disease that

in her fetus?

•

refractory

corticosteroids,

hydroxychloroquine,

and cytotoxics. Rituximab is a monoclonal antibody

What are potential complications of chronic

directed against B-lymphocyte CD20 surface antigens,

corticosteroid treatment in patients with SLE? •

drugs (e.g., rituximab and belimumab)

and belimumab is an antibody directed against the

Which drugs are associated with drug-induced

B-lymphocyte stimulator (BLyS) protein. It decreases

G R

lupus?

the amount of abnormal B cells, which are hypothesized

How does drug-induced lupus differ from SLE?

to be a mechanism of action in lupus. Specific use of these drugs is reserved for specialists.

PROGNOS IS I 0-year survival of systemic lupus is - 90% if patients

receive optimal treatment. Elevated anti-dsDNA and low complement levels indicate worse prognosis, with increased risk for nephritis. Elevated anti-U 1-RNP in the setting of a high-titer ANA and negative anti-Smith may indicate a better prognosis, because the disease may actually be mixed connective tissue disease (MCTD) and not SLE. Patients with SLE are also at higher risk for infections(due to immunosuppression), malignancy (especially hematologic ones), osteoporosis (secondary to glucocorticoids), and premature death from CAD(from disease inflammation and glucocorticoids).

TREATMENT OF SLE

9 9

Stress exacerbates SLE. Avoid surgery during active disease and encourage sunscreen to protect against the

ultraviolet-sensitive rash. Note that sunburn releases

self-antigens that are detected by the immune system and trigger a chain reaction to systemic flare! Tell your

h a

V d ti e n U DRUG�NDUCEDLUPUS

Classic drug-induced lupus (OIL) can be caused by procainamide,

hydralazine,

chlorpromazine,

propyl

thiouracil, phenytoin, and TNF inhibitors. Think about drug-induced lupus in any patient who develops consti

tutional symptoms (fever, arthralgias), serositis, and/ or rash while taking any of the above drugs. ANA is

positive and antihistone antibody is generally positive

(remember that SLE patients can have antihistone anti bodies, too!). In contrast to non-drug induced SLE, C3

and C4 usually are normal, anti-dsDNA is rarely positive, and there commonly is no kidney or CNS involvement. OIL can be a tough diagnosis to make. Ideally, you find: •

a positive ANA with antihistone antibodies, and

•

a history of exposure to one of the above drugs.

Sometimes you confirm the diagnosis only in retrospect by observing complete resolution of symptoms after discontinuing the drug.

patients to use sunblock of at least SPF 30 and reapply

Treatment: Symptoms usually resolve within 4-8 weeks

often. Tobacco cessation should be strongly encour

after stopping the offending agent, but the ANA may

aged-recent studies note that tobacco use can increase

remain positive for months. NSA!Ds and antimalarials

lupus disease activity.

may be useful. Corticosteroids work well but are only

Treatment of SLE is focused on the organ that is affected.

rarely needed.

Start with NSA!Ds for joint disease.(Remember, lupus arthritis is nonerosive.) Hydroxychloroquine is effective

SERONEGATIVE SPONDYLOARTHRITIS

for treating skin rashes and arthritis, and it can also help prevent disease flares.

"Spondylo-" means spine.

Seronegative spondyloar

Use high-dose glucocorticoids only for patients with

thritides are a group of inflammatory spinal arthritides that

severe disease and major organ involvement. Fatigue

are rheumatoid factor- and ANA-negative. These arthri

and alopecia may improve as well. Low-dose mainte

tides have been categorized as "axial" or "peripheral,"

nance corticosteroids(< 10 mg daily or every other day)

depending on which manifestation is primary in the

are frequently required to control symptoms and prevent

presentation. These include:

flares. Remember: Up to 113 of SLE patients on chronic high-dose glucocorticoids develop avascular necrosis of the hip/knee/humerus!

•

Ankylosing spondylitis(most common)

•

Reactive arthritis

•

Psoriatic arthritis

•

IBD-associated arthropathy

6-17

6-18

SERONEGATIVE SPONDYLOARTHRITIS

Seronegative spondyloarthritides share some common

Extraarticular manifestations of AS include:

features: •

Predilection for the spine, SI joints, and entheses (where the tendons, ligaments, and joint capsules

•

iritis/uveitis (about 1/3 of patients),

•

conjunctivitis,

•

ischemic heart disease,

•

aortic insufficiency/aortitis,

lower extremities

•

apical pulmonary fibrosis, and lgA nephropathy.

•

Extraarticular manifestations (see below)

•

Variable association with HLA-827

attach) •

Asymmetric, large-joint oligoarthritis, usually of the

Iritis or uveitis may precede sacroiliitis and usually

Enthesitis refers to inflammation at the insertion site of a ligament, tendon, or joint capsule. Enthesitis on the finger leads to the appearance of the "sausage digit." Note: The nail bed is also an enthesis; onycholysis (separation of the nail from the nail bed) is a sign of enthesitis in these diseases!

presents as unilateral pain, photophobia, and increased lacrimation. The uveitis associated with spondyloarthritis is typically an anterior uveitis where most of the inflam mation is localized in the anterior chamber of the eye;

G R

this is the opposite of what is seen in sarcoidosis, which features a posterior uveitis. Conjunctivitis may be mild and bilateral; progressive burning and eye irritation

Again, sacroiliitis and thoracolumbar and sacral spine

are prominent features. Apical pulmonary fibrosis is a

inflammation do not occur in RA! Sausage-shaped

late and rare manifestation that can be associated with

V d ti e n U

digits referred to as dactylitis are common in the

pulmonary restriction. IgA nephropathy is associated

spondyloarthropathies but not in RA. When the "sausage

with AS and should be suspected in any patient with AS

digit" buzzword is combined with "pitted nails," the

who develops an active urine sediment. These patients should be sent immediately to a nephrologist for renal

diagnosis is psoriasis!

biopsy.

ANKYLOSING SPONDYLITIS

Diagnosis

Overview

Ankylosing means "fusing," while spondylitis means "inflammation of the spine." Ankylosing spondylitis (AS) is a systemic disease marked by ascending axial

inflammation, which, if left untreated, leads to even tual spinal and SI joint fusion resulting in a radiographic

Inflammatory back pain has different characteristics

compared to other causes of back pain (e.g., disc dis ease). First, understand what the "regular" mechanical back pain looks like. Mechanical back pain usually is

characterized by the following: •

The patient is often obese, sedentary, and otherwise

•

A physical trigger (e.g., "Doc, I was lifting this box,

atic painful sacroiliitis, although for some patients, mild

•

Pain, often radicular and maximal at onset.

stiffuess is the only complaint.

•

Red flag and systemic signs are absent-by

bamboo spine (Image

6-7). Presentation and upper body

9 ri 9

"out of shape."

involvement increases with age. Patients have significant morning stiffuess/pain, which is improved with activity.

and it felt like I pulled something").

Most adults with ankylosing spondylitis have symptom

h ta

definition! (See Low Back Pain on page

Usual onset is in young adulthood with a peak age of

6-58.)

onset between 20 and 30 years, and it affects men more

Classic "inflammatory" back pain is a completely

than

different animal:

Teens

women

(2-3: 1).

eventually

diag

nosed with AS may pres

•

The patient can be young and otherwise

•

There is no known physical trigger.

in good shape.

ent with lower extremity large-joint

oligoarthritis

and have a

90% incidence

•

There is no radicular pain.

HLA-827-positive

•

The patient complains principally of stiffness,

•

Extraarticular manifestations (see above) are often

particularly morning stiffness.

antibodies. There

occurrence

only of

60%

present (if you take a stellar history!).

ankylos

ing spondylitis in identical

A useful bedside tool used in the physical examination

twins,

of a young adult male with inflammatory signs of low

environmental

factors also play a role.

back pain is the Schober test. This test assesses lumbar spinal mobility. Although it is not specific for AS, it is a sensitive measure in detecting limited spinal mobility.

Image 6-7: Bamboo spine; anky losing spondylitis

Plain radiographic signs of sacroiliitis (calcification and SI joint fusion resulting in the "bamboo spine"

SERONEGATIVE SPONDYLOARTHRITIS

Treatment remains controversial. Bottom line:

•

Systemic steroids are not recommended due to lack of efficacy and increased risk of osteoporosis and fracture.

•

Patients with primarily peripheral disease should be

•

Axial disease usually should be treated with a

given a trial of therapy with sulfasalazine.

How does a patient with ankylosing spondylitis

biologic drug, mainly anti-TNF agents. Know that

Which organisms are associated with reactive

the DMARDs sulfasalazine, methotrexate, HCQ, and

arthritis? •

NSAIDs are routinely recommended for analgesia

"Bamboo spine" is a buzzword associated with

present? •

•

and to reduce stiffness.

which disease? •

All patients should be on an exercise program.

What are common features of spondyloarthropathies?

•

leflunomide are not useful for axial disease.

What is the classic triad of findings seen in reactive

good, but more than

defonnity) may be absent for<

G R

If the diagnosis is made early, the prognosis is generally

arthritis?

10 years after onset of

20% of patients have progressive,

disabling disease.

in AS) that span at least 4 contiguous vertebral bodies.

V d ti e n U

The word "flowing" is used because these calcifications

responsible organism usually is not identified. While

symptoms. MRI is more sensitive and shows marrow edema in the bones adjacent to the Sl joints. Regardless, radiographic changes often are not seen at the time of diagnosis. The clinical and laboratory evaluations are most important in patients with early symptoms. sensitivity(> 90%), a negative HLA-B27 test is useful in excluding AS in patients. Because of its low specificity, it has little use in supporting the diagnosis of AS. A condition that can be confused with AS because of its radiographic appearance is diffuse idiopathic skeletal

hyperostosis (DISH). Classic x-ray findings in DISH include "flowing" osteophytes anterior to the spinal ligaments predominantly in the thoracic region (unlike

the ascending bamboo spine from the lumbar region

r i h

have the appearance of someone pouring candle wax in front of the vertebrae. Patients with DISH are rarely symptomatic, and the diagnosis is typically made as an incidental finding. In those who are symptomatic, "inflammatory back pain" symptoms are not present,

and patients can be treated with simple analgesics. Furthennore, DISH primarily occurs in men >

50 years

of age, does not affect the SI joint, and is not associated with HLA-B27. Inflammatory markers (ESR/CRP) are typically nonnal in DISH, but may be elevated in AS. DISH patients have a predisposition to developing diabetes mellitus.

Overview

The most common cause of acute, nontraumatic arthritis

HLA-B27 test is generally done. Because of the high

9 9

REACTIVE ARTHRITIS

in a person under the age of

in the body-typically genitourinary (GU) or gastro

intestinal (GI) infections. Common causes of reactive arthritis are a GU infection from

Chlamydia trachomatis Salmonella, Shigella, Yersinia, Campylobacter, and Clostridium difficile. GI causes of

and GI infections due to

reactive arthritis affect men and women equally, but GU causes predominantly occur in men

As we learn more about AS, treatment goals are changing. Traditionally, spinal and SI joint fusion was non-preventable, so the goal was to help the patients fuse their spines in a functional position. To some degree, this is still the goal, so main fonns of treatment include stretching exercises, posture training, and proper pillow positioning during sleep.(Sometimes no pillow is best.)

(9: l , M :F). It

is also seen in those with common viral illnesses (e.g.,

enterovirus) and HIV infection. The arthritis typically develops within 2 months of the infection, but the

reactive arthritis is the most common cause of an acute nontraumatic arthritis, it is a very uncommon cause of a spondyloarthritis-AS is more common. Reactive arthritis (ReA) most commonly presents as an asymmetric, mono- or oligoarticular arthritis of the lower extremities. Enthesitis is common and characteristic, especially at the insertion points of the Achilles tendon and the plantar fascia . Axial spine pain is not a common feature but occurs in about

20% of patients; thus, the

categorization of reactive arthritis as a spondyloarthritis. Extraarticular manifestations are common and include keratodenna

Treatment

50 is reactive arthritis, which

is an immunologic reaction to an infection elsewhere

tal

lesions,

blennorrhagicum, mouth

ulcers,

mucocutaneous

conjunctivitis,

and

geni iritis.

Keratodenna blennorrhagicum classically presents as papules/pustules with central erosion and characteristic crusting on the palms and soles and can be indistinguish able from pustular psoriasis. Circinate balanitis presents as an erythematous pustular or plaque-like lesion on the glans or shaft of the penis. The classic triad of urethritis, conjunctivitis, and asymmetric oligoarthritis is seen in less than 1/3 of patients.

6-19

6-20

SERONEGATIVE SPONDYLOARTHRITIS

Diagnosis can be tough because the inciting infection

a course independent of the bowel disease--symptoms

often is resolved when the arthritis presents. This is espe

do not worsen or improve in response to IBD flares or

cially true of the enteric pathogens. DNA amplification for

improvements.

genital Chlamydia is recommended in patients who have no obvious cause in their history, because Chlamydia infections can be asymptomatic, even in males. If a peripheral joint is swollen, arthrocentesis is recommended to exclude bacterial infection and crystalline arthropa thies. HLA-827 testing is not helpful. Radiographs are

Therapy for IBD (e.g., sulfasalazine, corticosteroids, azathioprine) may help control the peripheral joint symp toms and extraarticular manifestations. Anti-TNF agents are helpful in treating both peripheral joint and spinal symptoms.

helpful if osteoarthritis is a possible alternative diagnosis.

P SORIATIC ARTHRITIS Treatment

Arthritis with psoriasis is more often seen in patients

NSAIDs are recommended for initial treatment. Systemic steroids are used short-term in patients who have refrac tory peripheral arthritis. For severe or disabling disease, sulfasalazine or methotrexate is used. TNF inhibitors are used rarely and only in extreme refractory cases (Table 6-6 on page 6-12). The

use

antibiotics

treat

ReA

has

who have more than just the rash. 20-30% of patients nail from the nail bed), and "oil spots" (brownish dis coloration nails)

under

also

the

develop

joint

disease,

whereas

only

patients

V d ti e n U of

been

who

controversial. Some studies show benefits while others

rash

refute this claim. It is generally accepted that antibiotics

(Image 6-8). The rash is

simply

develop

have

arthritis

may be useful in treating the initial acute infection and

classically described as

may help prevent the development of ReA, but once the

salmon-colored plaques

arthritis has begun, long-term antimicrobial therapy is

on the extensor surfaces;

unlikely to modify the course of the disease.

however, in clinical prac-

ReA should be at the top of your list for any patient <

G R

who have nail pitting, onycholysis (separation of the

50 years old who develops an acute, asymmetric

tice the rash can be quite

Image 6-8: Dystrophic, pi!led nails in a patient with psoriasis

subtle.

large-joint arthritis in the setting of a recent gastrointes

Joint involvement in psoriatic arthritis can have varying

tinal or genitourinary infection. Quiz patients about any

presentations:

recent illnesses, especially diarrhea or urethritis/STD (usually during the prior 2-4 weeks), but also ask about

9 ri 9

viral infections and conjunctivitis.

lBO-ASSOClATED ARTHROPATHY

•

Symmetric polyarthritis: Looks like RA; can

•

Asymmetric arthritis (e.g., oligoarthritis): Usually

involve the PIPs, MCPs, knees. involves large joints like the knees, ankles, and

wrists; typically < 3 joints are affected.

IBD-associated arthropathy occurs in about 20% of

•

spondylitis with inflammatory back pain, but x-rays

patients with IBD and clinically manifests in 2 forms:

h ta

show an asymmetric sacroiliitis (unlike ankylosing

I) Asymmetric peripheral oligoarthritis of the lower extremities

extremities

peripheral occurs

with

oligoarthritis flare-ups

spondylitis and IBD-related spondylitis, where x-rays show a symmetric sacroiliitis).

2) Symmetric polyarticular arthritis of the hands Asymmetric

Spondylitis: Presentation is similar to ankylosing

the

•

lower

inflammatory

bowel disease, followed by complete remission of the peripheral synovitis as the bowel disease improves. The peripheral arthritis involves only a few joints in the lower extremities.

DIP arthritis: Looks like OA, but there is evidence of

nail psoriasis. •

Arthritis mutilans: There is severe resorptive

destruction of the joint. Patients can present with more than one pattern of joint involvement. For example, a patient with asymmetric oligoarthritis may also have spondylitis. Imaging is

Patients may also present with symmetric polyarticular

sometimes

arthritis of the hands, as seen in RA. However, recall that

from other forms of arthritis. Hand radiographs may

helpful

distinguish

psoriatic

arthritis

spondyloarthropathies are seronegative (negative ANA,

show a classic "pencil in cup" deformity, whereas in

RF, anti-CCP). Extraarticular manifestations such as

inflammatory OA, the classic finding is "gull wings"

erythema nodosum, pyoderma gangrenosum, and uveitis

(see Figure 6-1).

may also parallel the flare-ups of IBD.

Treatment: NSAIDs are 1 '' line therapy and are used

Axial skeleton involvement (- 20%) may be clinically

to control pain and inflammation. In patients with

and radiographically indistinguishable from AS and runs

symmetric or asymmetric arthritis, treatment is very similar to RA, with sulfasalazine being the predominant

OSTEOARTHRITIS

corticosteroids should also be avoided because their withdrawal can lead to a severe, life-threatening form of pustular psoriasis. Other conditions that exacerbate psoriasis include skin trauma, sunburn, viral infections, •

and strep pharyngitis.

What are the patterns of arthritis seen with psoriasis? Name some other associated features.

•

Which drug, sometimes used in treatment of arthritis, might exacerbate the psoriatic rash?

SUMMARY Sausage-shaped digits are common only in reactive

"Sausage-shaped digits" are seen in which

arthritis and psoriatic arthritis. Ice pick-like pitting of the

arthritides?

nails is very specific for psoriatic arthritis. Causes of DIP

•

What is the pattern of arthritis in osteoarthritis?

and PIP synovitis are limited (reactive and psoriatic only).

•

Which joints are typically spared in primary

•

osteoarthritis? •

•

OSTEOARTHRITIS

Which joints of the hand are affected in primary osteoarthritis? What characteristic features are

Osteoarthritis (OA) is, by far, the most common form

seen in the hands of patients with OA?

of arthritis. It can be primary (idiopathic) or secondarily

What diagnoses do you consider when you see the pattern of DIP and PIP swelling?

crystalline arthropathy comes first, although most experts

DMARD used in patients with disease refractory to NSAIDs. Anti-TNF agents are reserved for patients with spondylitis and for those with moderate-to-severe arthritis failing to improve with DMARD and NSAID therapy.

Paradoxically,

there

have

been

increased

numbers of reports showing an increase in psoriasis in RA patients who are treated with anti-TNF drugs. The rash resolves with topical steroids or discontinuing anti-TNF therapy. Another drug that is useful for the treatment of psoriatic arthritis is cyclosporine A, which may be used to control both the joint and skin disease (monitor renal function and blood pressure). Avoid antimalarial drugs (e.g., hydroxychloroquine), lithium, and beta-blockers in psoriatic arthritis because they

often

exacerbate

the

skin

associated with other inflammatory arthritis, such as gout and pseudogout. It's unclear whether the OA or the

disease.

Systemic

think the latter. OA also can arise after joint damage due to hemochromatosis, trauma, RA, or neuropathic joints related to diabetes. OA pain characteristically worsens with excessive activity and has an insidious progression (contrary to the inflammatory arthritides, such as gout and RA). The joint damage of OA is classically nonerosive (although there is a rare erosive variant of OA), asymmetric, and without calcium deposition in the car tilage (termed "chondrocalcinosis"). Most commonly affected joints are carpometacarpal (CMC-1) joints of the hands, feet, knees, hips, and the spine. Involvement of the ankle, wrist, and elbow is very rarely due to OA. If a patient's symptoms include swelling of one of these 3 areas, consider pseudogout, gout, RA, or other inflammatory arthritis-not OA! OA of the hands: Changes most often affect PIPs and

DIPs and may be associated with classic enlargements called Bouchard (PIP) and Heberden (DIP) nodes. There is controversy about whether the nodes result from osteophyte formation or development of small cysts around the joints. The enlargement of the hand joints is typically asymmetric, hard, and bony-not soft and spongy, as with inflammatory arthritis. Occasionally, though, these DIP and PIP nodes can become inflamed and very tender, mimicking the inflammatory joint dis ease of psoriatic arthritis. (Remember, though, that psoriatic arthritis often has nail involvement whereas inflammatory OA does not.) Erosive OA is another term for inflammatory OA; x-rays can reveal evidence of ero sions at the DIP joints, where formation of"gull wings" are classic findings. The CMC-1 joints at the base of the thumbs can be involved; "squaring" of the CMC-1 joint is a common physical finding. Note that OA rarely Figure 6-1: Osteoarthnt1s. gull w1ng deformity: Psonat1c arthnt1s pencli-m-cup deform1ty

MedStudy

affects MCPs (metacarpophalangeal joints).

6-21

6-22

OSTEOARTHRITIS

DIP:

Psoriatic arthritis Osteoarthritis (Heberden nodes)

PIP:

Osteoarthritis (Bouchard nodes) Rheumatoid arthritis SLE

MCP: Rheumatoid arthritis SLE

Hemochromatosis

Figure 6-2: Hand Jomts Affected by Rheumatologic D1seases

To review: Remember that OA involves the DIPs

3) Fewer than 3 MCP swellings

and PIPs, but not the MCPs, which is seen in RA!

4) Deformity of I of the IO DIPs/PIPs

(See Figure 6-2.) Diagnosis of hand OA is supported when there is pain in the hands with 3 of the following clinical criteria (sensi tivity 94%; specificity 87%):

Hip OA: Pain is usually worse with weight bearing and

in the groin area (as opposed to the lateral thigh, which is more often seen with trochanteric bursitis) , but it can

1) Bony enlargement of2 or more: DIPs/PIPs of2"d and 3'd fingers and 1+ carpometacarpal joints

also be experienced as radiation to the knee. Diagnosis is supported by hip pain and 2 of the criteria below (and exclusion of other diagnoses):

2) Bony enlargement of> 2 DIPs

I) ESR < 20 mm/hr 2) Femoral or acetabular osteophytes on radiograph 3) Joint

space

narrowing

on radiograph

(superior

migration) Radiographs and labs do increase diagnostic sensitivity and specificity

(89% and 91% respectively, if these

criteria are used). Knee OA: Pain is usually worse with prolonged weight

bearing and characterized as a deep ache superior to the patella or deep inside the knee joint. Pain described as medial and inferior to the joint is more likely to be from pes anserine bursitis. And don't forget that pain from hip OA can radiate to the knee. (See Image 6-9.) Suspect knee OA when the case includes pain and several of the following features: •

•

Image 6-9: Standing radiographs of the knees showing severe OA with loss ofjoint spaces

•

Age usually 2: 50 years Obesity Morning stiffness < 30 minutes

CRYSTAL DEPOSITION ARTHRITIDES

Acute gout usually

presents after

10-30 years of

sustained hyperuricemia-in male patients

40 years of

age and after menopause in females (estrogen appears to be a uricosuric agent). Comorbidities and certain drugs •

•

Characterize the joint synovial fluid in patients with OA.

can increase the risk for gout. The following have been linked to gouty arthritis:

At what age does acute gout usually present?

•Intake of beer or liquor (not wine)

•Bony enlargements (especially if age is < 40 years) •Knee malalignment: hallux valgus (knock knees) or hallux varus (bow-legged)

•Soft drinks/fructose consumption •Surgery

•Noninflammatory synovial fluid

•Starvation/Dehydration

(200-2,000 WBCs/mm3) <

and seafood •Trauma

•Crepitus

•ESR

•High intake of fatty foods, organ meat, red meat,

•Drugs: thiazide and loop diuretics, nicotinic

20 mm/hr

acid, low-dose aspirin, tacrolimus, cyclosporine,

•Osteophytes on radiograph

ethambutol

The more data you have in combination, the more confident you can be about an OA diagnosis. Clinical

Factors associated with reduced gout flares:

criteria alone are about 90% sensitive and specific

•Caffeine

(higher with labs and radiographs).

•Vitamin C (be careful of oxalosis when using vitamin

Treat knee OA with education (weight loss, exercise, and shoe insoles) and analgesics for pain relief (acetamino

C in patients with chronic kidney disease) •Dairy intake (at least 2 servings/day)

phen at maximum dose of 4 g/day and/or NSAIDs).

Excess uric acid (UA) is caused by either decreased

Tramadol alone, or in combination with acetaminophen

renal excretion (underexcretors; 90%), its increased

+/- NSAID or celecoxib, is helpful for refractory pain.

production (overproducers; < I 0%), or a combination

Long-term opiates should be minimized, especially in

of the two. Again, most cases (90%) of gout are due

the elderly.

to decreased renal excretion. Note that most patients

Intraarticular

glucocorticoids

are

useful

patients

unable to tolerate NSAIDs, receive inadequate analgesia

with

hyperuricemia

never

develop

gout, tophi,

nephrolithiasis!

from acetaminophen, and/or have only I or 2 painful

Hyperuricemia can be primary, in which case it is usually

joints. Limit intraarticular steroid injections to no more

permanent, or it can be secondary, as a result of comorbid

than 3-4 a year.

diseases or drugs.

Viscosupplementation with intraarticular injection of

Decreased renal excretion of uric acid can be idiopathic

hyaluronic acid may also be effective in reducing pain in

or secondary to:

some patients, although a recent metaanalysis suggested it had limited efficacy. Some patients who do not respond to intraarticular steroids may respond to hyaluronic acid. Watch out for post-injection flares. Randomized, placebo-controlled trials and metaanalyses have shown no difference in pain with glucosamine + chondroitin. If the patient does not respond to the above therapies, knee replacement is indicated.

•chronic renal disease, •lead nephropathy, •alcohol, •drugs, or •diabetic ketoacidosis. Increased production of uric acid can be idiopathic, or secondary to: •leukemia, •hemolytic anemia,

CRYSTAL DEPOSITION ARTHRITIDES GOUT Gout is caused by an excess of uric acid in the serum with deposition of monosodium urate crystals into joints, causing recurrent bouts of acute arthritis and, ultimately, chronic arthropathy. Crystals also can accumulate in tissues, causing tophi and kidney stones.

MedStudy

•tumor lysis syndrome, •psonasts, •exerctse, •fructose ingestion, or •G6PD deficiency. To determine whether a patient is an "underexcretor" or an "overproducer," measure the amount of UA in the urine over 24 hours. Underexcretors have low-to-normal 24-hour urine UA levels in the setting of increased

6-23

6-24

CRYSTAL DEPOSITION ARTHRITIDES

serum levels (or >

600 mg); overproducers often have

800 mg per 24 hours.

the diagnosis.

Definitely do these measurements in premenopausal females and in males

finding a floating uric acid crystal does not make gout Rarely, monosodium urate crystals are not identifiable in

25 years of age who develop

the joint fluid, and the fluid characteristics can make this

acute gout. (Often the hyperuricemia is hereditary, and

presentation hard to differentiate from septic arthritis.

many get kidney stones.) Also, do these measurements

In that situation, gout is the most likely diagnosis if

if you intend to prescribe a uricosuric agent, to ensure

the patient has evidence of uric acid deposition in the

that the patient's rate of elimination won't result in stone

tissues (e.g., linear densities overlying cartilage visible

formation if you increase the excretion rate with drug

on ultrasound; uric acid deposits visible on CT; and

intervention. In most other cases, these measurements

subcortical bone cysts visible on plain radiographs or

usually are not performed because they rarely result in a

MRI indicative of bony tophi). Always send the joint

change in management.

fluid for routine Gram stain and culture because gout can

Acute gouty arthritis classically presents as an acutely

coexist with infection.

tender and swollen joint that may occur at night and

It is important to know that a rapid decrease or, less

awakens the patient from sleep. Pain reaches maximum

commonly, an increase in uric acid level is thought to

intensity within the first 24 hours and self-resolves within

precipitate gouty attacks. The uric acid level does not

a few days to several weeks. In 50% of patients, the

correlate with an attack of acute gout-often patients

initial attack occurs in the metatarsophalangeal (MTP)

have normal or low levels when the acute arthritis is

joint of the great toe (termed "podagra"). The knee is the

present. Conversely, an elevated serum uric acid does

next most commonly affected joint. In the early stages

not confirm the diagnosis of gout, but it does indicate

of gout, the patient is completely asymptomatic between

patients who are at risk. As serum UA levels increase

attacks ("intercritical period")-a useful clue to help

distinguish gout from other arthritides if the diagnosis

5% per year.

is in question. With chronic tophaceous gout, patients often have symptoms between flares.

9-10 mg/dL, incidence of gouty attacks increases to

Quick review: Gout

intracellular monosodium urate

crystals, needle-shaped, yellow when parallel, negative

Acute polyarticular gout is much less common. It is more

birefringence.

often seen in patients with myelo- or lymphoproliferative disorders

(e.g.,

leukemias),

post-organ

transplant,

chronic kidney disease, and longstanding disease. Diagnose gout by performing an arthrocentesis and looking for intracellular crystals in the joint fluid. Arthrocentesis classically shows inflammatory joint

Acute Treatment NSAIDs, corticosteroids,

or oral colchicine are all

appropriate I st line agents for acute gout. Know that the earlier any treatment is initiated the better the response.

2,000 WBCs/mm3 and a predominance of

Treat the acute attack with ice packs and consider

neutrophils. Monosodium urate crystals are "needleÂ

intraarticular corticosteroids if only I or 2 joints are

fluid with

shaped" and are strongly negatively birefringent under

involved and suspicion for infection is low. Use NSAIDs

polarized light. (The crystals that are parallel to the

or colchicine if multiple joints are involved and if there

color compensator are yellow.) To be diagnostic, the crystals must be intracellular. See I mage 6-10. It is very important that the crystals be seen inside cells before gout is considered as the cause of an acute arthritis. Occasionally, urate crystals are found floating in the joints of patients who do not have gout. So, merely

are no contraindications. Traditionally, indomethacin has been the choice NSAID for the treatment of gout, but anyNSAID, including a COX-2 inhibitor, will work. Low-dose oral colchicine (1.2 mg x I

dose, then

0.6 mg I hour later) followed by prophylactic doses if needed can be used in patients instead ofNSAIDs. This low-dose regimen has equivalent efficacy and better GI tolerability when compared with the older, higher-dose regimen (e.g., 1.2 mg followed by 0.6 mg every hour for 6 hours). Side effects of colchicine typically are nausea, vomiting, and diarrhea, but myopathy and bone marrow suppression can be seen with long-term use, especially in patients with advanced chronic kidney disease. IV colchicine is no longer available in the U.S. because of its side effect profile. Cmticosteroids are especially useful for patients when NSAIDs or colchicine are contraindicated or ineffective. Either local steroid injections or systemic therapy are effective, but exclude infection first.

Image 6-10: Uric acid Clystals under polarized light

ÂŠ 2014

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

CRYSTAL DEPOSITION ARTHRITIDES

Prescribe ULT to patients with the following: o

Tophi Uric acid kidney stones or 24-hour urine uric acid level > 1,100 mg/day (but do not use a uricosuric drug)

How is gout definitively diagnosed?

Characterize the crystals of gout when observed under a polarizing microscope.

Radiographic signs of chronic gouty arthropathy

Recurrent acute attacks (> 1/year)

Xanthine Oxidase Inhibitors

How could you treat a gout flare in a single joint?

What drugs used for chronic treatment of gout are

First-line ULTs are the xanthine oxidase inhibitors

contraindicated during an acute gouty attack?

(XOis), which include allopurinol and febuxostat. These

agents reduce SUA in both underexcretors and over

What is the goal uric acid in a patient who has more

producers. Remember that underexcretion of UA is the

than 1 attack of gout a year? o

most common cause of hyperuricemia.

With which drugs do you have to adjust the dose

Allopurinol is the most commonly prescribed XOI. It

of allopurinol downward?

is cheap and effective. Common side effects include

Commonly used is prednisone or methylprednisolone as monotherapy or in combination with colchicine. Note that the combination of steroids and NSAIDs increases the risk of gastric toxicity. Antihyperuricemic drugs that are given for chronic treatment of gout (e.g., allopurinol, febuxostat) should not be started during an acute gout attack, but should be continued if the patient is already taking the drug.

nausea, vomiting, and diarrhea. Allergic reactions can occur, ranging from a simple drug rash to rarely fatal hypersensitivity reactions: toxic epidermal necrolysis ( TEN)/Stevens-Johnson syndrome (SJS). TEN/SJS is manifested by fever, acute kidney injury, eosinophilia, liver dysfunction, blistering mucosa, and typical TEN/SJS rash. Patients with impaired renal func tion are at greater risk for developing hypersensitivity reactions. For this reason, recent guidelines recommend that the starting dose of allopurinol should not exceed 100 mg/day. In those with moderate-to-severe kidney

Chronic Treatment

disease, the starting dose should be even lower (e.g.,

Overview

50 mg/day).

The goal of therapy should be to reduce uric acid load and to prevent a subsequent attack. Chronic treatment of gout includes:

Dietary/lifestyle

More recently, a strong association has been discovered between HLA-8*580 1 and allopurinol-related

TEN/

SJS. Screening for this gene has been suggested prior

modifications.

Avoidance

precipitants, including the foods and drugs previously mentioned on page 6-23, may not be practical or may be adhered to poorly. Patients should be counseled on low purine diets and alcohol avoidance, which can lower the frequency of acute gout attacks, but may not be effective long term in lowering UA levels(e.g., decline� 1 mg/dL). In addition, many patients do not adhere to dietary mod ifications given that these are less palatable than their

to initiation of allopurinol; however, due to cost and availability of the test, testing may not be practical. Another important item to know about allopurinol is that the dose must be decreased by 66--75% in patients taking azathioprine or mercaptopurine. Because metab olism of these drugs is inhibited by XOis and can lead to increased drug toxicity such as bone marrow suppression, labs should be monitored closely.

usual diet. The best diet is simple caloric restriction with

Febuxostat is much more expensive than allopurinol.

an emphasis on complex carbohydrates (in lieu of pro

Side effect profiles are similar to allopurinol; the drug

cessed simple sugars}-the goal is to effect weight Joss,

is useful in patients who cannot tolerate allopurinol,

which does lower the incidence of gout.

including those with drug hypersensitivity to allopu

Urate lowering therapy (ULT). The goal of ULT is to reduce the serum uric acid (SUA) to < 6.0 mg/dL, which is below the saturation point of monosodium urate. [Know this!] When SUA levels are < 6.0, urate crystals are reabsorbed from the joint and tophi, resulting in

rinol. Reduction in uric acid is rapid with febuxostat, and there is no need to adjust dosage for a glomeru lar filtration rate (GFR) below 30 cc/min. Avoid using febuxostat with azathioprine or mercaptopurine because it is a more potent XOI than allopurinol.

reduction in frequency of gout flares. Patients with tophi

Also note that both allopurinol and febuxostat can reduce

and more severe disease would benefit from an even

the clearance of theophylline, which increases theophyl

lower serum uric acid level (< 5.0 mg/dL). Remember:

line levels. Monitor theophylline levels in patients who

Start chronic treatment after the acute attack resolves

are on concomitant therapies with XOI and theophylline.

completely and titrate dose to goal uric acid.

6-25

6-26

CRYSTAL DEPOSITION ARTHRITIDES

Uricase

Chronic Treatment Summary

Uricase is an enzyme that oxidatively degrades uric acid to soluble allantoin that can be readily excreted. Humans and higher primates lost uricase expression during the course of evolution. Rasburicase is a uricase approved for tumor lysis syndrome and has been shown to help reduce tophi burden in patients with chronic tophaceous gout; however, the drug is not FDA-approved for gout because it is highly antigenic and has poor tolerability and sustainability.

I) Decrease red meat and fish. Increase other proteins. Decrease carbohydrates. Decrease alcoholic drinks.

Pegloticase, a pegylated recombinant mammalian uricase, was approved by the FDA for use in refractory tophaceous gout. The drug has less immunogenicity, but infusion reactions and anaphylaxis are still concerns.

2) Control H TN. 3) Start treatment with an XOI. Allopurinol is the drug of choice. Give febuxostat if patient is unable to tolerate allopurinol or if allopurinol is not effective.

4) Use pegloticase for symptomatic tophaceous gout not controlled by an XOI. 5) Give low-dose cholchicine until 3-D months after urate levels return to normal. Gout Pearls Know the following!

Uricosuric Agents

•

Uricosuric agents inhibit urate transporter URATI to increase uric acid renal clearance; these agents are rarely used due to poor adherence. Probenecid, the only uri cosuric approved in the U.S., requires multiple daily doses and ingestion of> I gallon of water/day to prevent uric acid renal stones. It is considered a 2"d line agent in underexcretors who are resistant/intolerant to XOis. Probenecid should be avoided in patients: •

•

Who are overproducers or underexcretors of uric acid With history of renal stones With tophi With renal insufficiency where GFR :S 30 cc/min or Cr> 2.0 mg/dL, because the drug would be ineffec tive given its mechanism of action

Though its use as a monotherapy drug may be limited, new gout guidelines suggest that adding a low-dose uricosuric agent to an XOI may be a means to reach target uric acid goal.

•

Use Acute Gout Prophylaxis While Lowering Uric Acid

•

The risk for an acute gout attack is high when ULT is initiated. Remember, a rapid increase or decrease in uric acid level can precipitate gouty attacks. To lower the rate and severity of flares during ULT, the American College of Rheumatology (ACR) recommends that patients receive pharmacologic antiinfllammatory prophylaxis with low-dose colchicine(0.6 mg qd to bid) or NSAIDs (with a PPI when indicated). If colchicine or NSAIDs are not tolerated, are ineffective, or are contraindicated, then low-dose prednisone(< 10 mg/day) can be consid ered. Prophylactic therapy should be continued for at least 6 months if tophi are present, 3 months if there are no tophi.

Low-dose aspirin(e.g., :S 325 mg/day) interferes with urate excretion. High-dose aspirin(e.g.,::=: 1-3 g/day) causes uricosuria. Therefore, at commonly used doses, aspirin interferes with UA excretion. Differential Dx for acute monoarticular joint swelling infection vs. crystalline vs. fracture/trauma. Gout can cause fever. Premenopausal women rarely get gout.(Estrogen is a uricosuric.) Older women may present with polyarticular pseudo-rheumatoid crystalline arthritis(gout or pseudogout that presents similarly to RA). So, think of gout or pseudogout in the older woman who looks like she has suddenly developed RA. Always look for crystals in joint fluid! Gouty joint radiographs may have a characteristic erosion with an overhanging edge, termed marginal erosion or "rat-bite" erosion that is caused by a tophus. RA and gout rarely coexist. Acute gout +joint infection is uncommon, but should never be missed. Goal uric acid should be < 6.0 mg/dL; for patients with tophi, the goal uric acid should be < 5.0 mg/dL. Give antiinflammatory prophylaxis while lowering uric acid to prevent flares.

•

CPPD DEPOSITION DISEASE Calcium pyrophosphate dihydrate (CPPD) crystals cause chondrocalcinosis (calcium in the cartilage) and subsequent damage to joints. Most idiopathic CPPD deposition occurs in patients > 65 years of age and who have underlying joint damage from OA or trauma. However, when you see CPPD deposition in a patient < 50 years of age, consider these predisposing conditions: •

•

Primary hyperparathyroidism Hemochromatosis(see Hemochromatosis Arthritis on page 6-32)

CRYSTAL DEPOSITION ARTHRITIDES

CPPD crystals dissolve and change their birefringence when stored

12-24 hours, so analyze the fluid imme

diately. Urate crystals are much less likely to dissolve. If your fluid cannot be examined within a few hours, •

•

Inflammatory arthritis of certain joints should make

refrigerate it to slow the decomposition of crystals and

you think of CPPD disease. Which joints are they?

white cells.

What do CPPD crystals look like under polarized

Quick review: CPPD crystals =rhomboid, positive bire

light?

fringence (light blue when parallel), chondrocalcinosis.

Which diseases are associated with CPPD?

Management of acute arthritis is extrapolated from gout data and is essentially identical to the treatment of acute gout. First-line therapy would be joint aspiration and

•

Hypothyroidism

•

Hypomagnesemia

tion. Colchicine can be used but may be less effective.

•

Hypophosphatemia

Use oral prednisone if patients have refractory disease

NSAIDs and/or intraarticular glucocorticoid administra

The presentation ranges from asymptomatic deposition of crystals in joint cartilage (visible only on radiographs) to an acute monoarticular arthritis (often referred to as "pseudogout," similar to uric acid gout) to presentations similar to OA and RA. Chondrocalcinosis is calcification of cartilaginous tissue and is a hint to underlying CPPD, so think of this diagno sis if you're shown obvious calcifications in the cartilage on a radiograph of a small joint. If the presentation is one of an acute arthritis, the arthrocentesis usually reveals an inflammatory joint fluid (WBCs

2,000 cells/mm3)

with an excess of neutrophils, some of which will contain CPPD crystals. CPPD

arthropathy

usually affects the knee. Other

common joints affected by CPPD include wrists, 2"d and

3'd MCPs, shoulders, elbows, and ankles. Recall from the OA section, we said that OA rarely involves these joints! If your patient has wrist synovitis in the face of OA, first think CPPD deposition-not OA only! Also, when chondrocalcinosis is visible on radiographs of the

or are unable to take NSAIDs/colchicine. Low-dose col chicine also can be used as prophylaxis for acute attacks. There is no equivalent drug to XOI in CPPD disease that can reduce the burden of crystals in the joints. However, in patients with associated metabolic conditions (e.g., hemochromatosis), treatment of the underlying disease may decrease the number of attacks. In hemochromato sis, phlebotomy may not change the joint calcification, but other manifestations of the disease, such as diabetes and liver disease, can improve. Again, look out for the patient with wrist arthritis who also has Bouchard (PIP) and Heberden (DIP) nodes consistent with OA-think CPPD and screen for hemo chromatosis, hyperparathyroidism, and hypothyroidism in patients younger than

50 years of age.

HYDROXYAPATITE ARTHROPATHY Hydroxyapatite arthropathy (HAA) also is known as basic calcium phosphate arthropathy or calcium apatite deposition disease. Hydroxyapatite is the primary min

wrists or MCPs, think CPPD.

eral in bone and teeth. Abnormal accumulation may

Diagnose CPPD by finding intracellular crystals that

occur idiopathically; in hypercalcemic/hyperparathy

are blunted, rhomboid, and are weakly positively bire fringent under polarized light. (Crystals are light blue when parallel to the color compensator.) See examples of intracellular and extracellular CPPD crystals in Image

6- I I and I mage 6-12. Recall: Uric acid crystals

are needle-shaped and are strongly negatively birefrin gent (bright yellow when parallel to the compensator). Be able to distinguish uric acid and CPPD crystals from photomicrographs (based on color) and from descrip tions of the crystals.

roid states; in damaged tissues; and in scleroderma and dermatomyositis. Crystal arthropathy in dialysis patients is sometimes due to HAA and both CPPD and HAA are ,

associated with OA. The most common joint affected is the shoulder. Think about HAA in elderly patients (especially women) who have a destructive arthropathy of the shoulders ("Milwaukee shoulder"), hips, knees, and/or hands with noninflammatory synovial fluid (increased mononuclear cells) and no visible crystals. Radiographs show calcifi cation in and around the joints +/- erosions, depending on how bad the disease is. Confirm diagnosis of HAA arthropathy with identi fication of the HAA crystals in the joint fluid. Unlike urate and CPPD crystals, these crystals are very small, nonbirefringent, and can be seen only by electron microscopy or light microscopy with special staining (using alizarin red, done by pathologists).

Image 6-11: CPPD crystal; extracellular

MedStudy

Image 6-12: CPPD crystal; intracellular

6-27

6-28

INFECTIOUS ARTHRITIDES

Treatment for acute HAA is the same as for acute CPPD.

Know these septic joint associations and portals of entry

For dialysis patients, controlling serum phosphorus

that allow dissemination of the bacteria (Table

levels helps prevent flares. •

6-7):

S. aureus >> S. viridans =usual cause (60-70%) of septic native joints in adults, especially in RA patients. Portal of entry: skin, wound infection.

INFECTIOUS ARTHRITIDES •

gonorrhoeae

age group!) often with concomitant Chlamydia trachomatis. Remember that synovial WBC counts

Overview are

(most common cause of infectious arthritis in this

SEPTIC ARTHRITIS

There

Adolescents and young adults

classifications

nongonococcal (organisms other than

septic

may be in only the 10,000 cells/mm3 range. Portal

arthritis:

of entry: oropharynx and genitourinary tract.

Neisseria gonor

rhoeae) and gonococcal arthritis.

•

pneumococcus, but staph is still most common.

Septic (bacterial) arthritis is inflammatory and usually

Portal of entry: bloodstream due to asplenia.

monoarticular, occurs from seeding during bacteremia, and is associated with fever. In most cases, joint aspirate is inflammatory (average WBCs

= 100,000 cells/mm3)

with predominance of neutrophils, and a Gram stain fre

•

Human bites= anaerobes and Eikenella.

•

Animal bites

•

Extensive comorbidities

gram negatives, group A

•

Indolent, chronic, and with noninflammatory fluid

•

Injection drug users= staph, strep, gram negatives

(+/-bloody)= mycobacteria, fungus, or noninfectious.

mycobacteria or fungi as etiologies, or a noninfectious cause of arthritis.

=Pasteurella multocida.

streptococci, pneumococcus.

quently shows the infecting organism, but not always. An indolent history with noninflammatory fluid suggests

Sickle cell anemia= Salmonella and

(especially

Pseudomonas); predilection for axial

disease (e.g., sternoclavicular and sacroiliac joints). '

Table 6-7: M1crob1al Causes of Sept1c Arthritis

Adolescents, adults

Main Trait

Port of Entry

Bacteria

Host

gonorrhoeae

WBC in joint usually lower than typical septic joint. Can be 10,000 cells/mm3•

Chlamydia can coexist;

joint cultures usually negative Children, adults

aureus

Skin/wound infection

Children, adults

Accounts for 2/3 of all septic arthritis

Anaerobes

Eikenella spp. Children, adults

Pasteurella spp.

Animal bites

Cat bite wounds

Sickle cell patients

aureus Salmonella spp.

Hematogenous

Infection can precipitate a sickle cell crisis

Pneurnococcus spp. Patients with prosthetic joints

aureus

Hematogenous, local wound

Coagulase-negative staph

Loosening of prosthesis concerning for infection

infection Injection drug users

Staph, strep, gram-negative bacteria

Patients with many

Gram negatives, staph, group A

comorbidities Immunosuppressed

strep, pneumococcus

Respiratory,

Get blood cultures as well

hematogenous

Mycobacteria, fungus

patients

Fisherman, aquarium hobbyist

Mycobacterium marinum

Local wound infection

Cultures may be negative from synovial fluid, need culture from mucosal surfaces

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INFECTIOUS ARTHRITIDES

Nongonococcal Arthritis In nongonococcal septic synovitis, the joint is hot and tender, and the patient may be febrile. Try to get blood •

cultures and aspirate your joint fluid before administer

What is the typical cell count in the synovial fluid

ing antibiotics. Fluid is inflammatory, and Gram stain

of a septic joint? Which type of cells are they? •

of the joint fluid usually shows WBCs and organisms. Fluid cultures grow the organism most of the time, and

What are common pathogens associated with septic joints?

about half the time, blood cultures are also positive. Direct inoculation of blood culture vials with joint fluid

•

How do you diagnose gonococcal arthritis?

•

What is special about the approach to diagnosis

may increase the likelihood of isolating the organism, although studies are divided about whether or not direct

of gonococcal arthritis compared to traditional

inoculation makes a difference.

septic joint workup?

•

Treatment

Prosthetic joints= S. aureus or coagulase-negative staph; "loosening of the prosthesis" is very concerning for infection.

for

septic

arthritis

includes

systemic

antibiotics targeted to the Gram stain result: nafcillin or vancomycin for gram-positive cocci; broader coverage for gram negatives, pneumococcus, and gonococcus if no organisms are seen; and antipseudomonal coverage if injection drug use is suspected. Repeated drainage of the

Gonococcal Arthritis

joint may be necessary. Patients who don't improve with

Pregnancy and menstruation are predisposing factors

antibiotics and repeated aspiration should go for laparo

for disseminated gonorrhea. Patients with deficiency

scopic or open lavage. Intraarticular antibiotics are not

of terminal complement components are also at high

recommended.

risk. Presentation

Patients who have prosthetic joints but need to undergo

is fever,

migratory

polyarthritis,

tenosynovitis, and dermatitis (red papules that become pustular). Gonococcal joint infection is always from dissemination, but you might have missed the clinical signs/symptoms during dissemination. Remember to consider this diagnosis in the adolescent with knee pain.

procedures (e.g., dental, urologic) are at risk for devel oping transient bacteremia and seeding of their joint. However, there is no evidence to recommend routine antibiotic prophylaxis in patients with prosthetic joints undergoing invasive dental, GU, or GI procedures.

In gonococcal arthritis, arthrocentesis often reveals a WBC count

50,000 cells/mm\ but it may be as low

as I 0,000--20,000. Joint cultures are usually sterile and blood cultures are positive in

50% of cases.

Know that in disseminated gonorrhea, you culture all mucosal surfaces that could be harboring the organ ism (i.e., cervix, rectum, and oropharynx in women; urethra, rectum, and oropharynx in men), in addi tion to any

skin

gonorrhoeae

susceptible

light, and other

lesions, is

joint fluid,

relatively

temperature

fragile

changes,

environmental

and

blood.

organism,

drying,

stresses.

Strains of

N. gonorrhoeae are fastidious and variable in their cultural requirements, so that media containing hemo globin, NAD, yeast extract and other supplements are

Acute Rheumatic Fever Acute rheumatic fever (ARF) is a rare immunologic complication that typically occurs

Polyarthritis is one of the World Health Organization's criteria for diagnosis. Consider ARF in adolescents and young adults (rare after age The Jones criteria

(2 major, or 1 major and 2 minor)

should be viewed as a guide to determine who is at high risk but cannot be used to define diagnosis with abso lute certainty. An exception includes chorea, which can present as the sole manifestation of ARF, in spite of negative laboratory results.

Therefore, adequate cultures require direct plating of

Jones major criteria-CCEPS:

the specimen on Thayer-Martin ("chocolate") agar at media before you do an arthrocentesis. Then, squirt some of the joint fluid directly onto the chocolate agar

•

of sending joint fluid for gonococcal PCR, do that the results are highly sensitive. The aggregate yield of

Carditis (e.g., prolonged PR interval) Chorea Erythema marginatum (pink macules with central clearing, typically on the trunk)

plates-in addition to sending the fluid for routine Gram stain, culture, and sensitivity. If you have the option

•

Polyarthritis (typically migratory) Subcutaneous nodules (painless)

Jones minor criteria:

detecting the pathogen by culturing all mucosal sites is

70--90%. In contrast, blood, synovial, and skin cultures

•

are typically negative.

•

Fever, arthralgias. A throat culture positive for Streptococcus is found in approximately presentation.

MedStudy

30) who fulfill the ARF

criteria (below).

needed for isolation and growth of the organism.

the bedside. So, go to the lab first and get your special

1-5 weeks after

a previous group A beta-hemolytic strep infection.

25% of patients at the time of

6-29

6-30

INFECTIOUS ARTHRITIDES

WHIPPLE DISEASE

Treatment is the same as for active pulmonary TB:

Whipple disease is a rare and chronic bacterial infection caused

Tropheryma

whipplei.

predominantly

affects white, middle-aged men (M > F 4: 1) and causes recurrent

episodes

nondestructive

seronegative

isoniazid, rifampin, pyrazinamide, and ethambutol x 2 months-until you get the organism and its sensitivi ties. Then, narrow therapy to 2 drugs x 4-7 more months (6-9 months total). Treat longer if the patient is HIV+.

inflammatory arthritis that predominantly affect large joints (e.g., knee). It is also commonly associated with Gl manifestations including diarrhea, malabsorption, and weight loss, fevers, lymphadenopathy, skin hyperpig mentation, and neurologic findings. The main neurologic symptom is memory loss due to a slowly progressive

VIRAL ARTHRITIS V iral diseases can cause a true infection of the joint (aseptic arthritis) or a reactive (immunologic) arthritis (previously discussed on page 6-19).

dementia. "Oculomasticatory myorhythmia" (conver

Patients

gent-divergent nystagmus with concomitant masticatory

pseudo-RA

contractions) is pathognomonic for Whipple disease.

therapy (NSAIDs) and typically does not recur.

Importantly, the joint manifestations usually precede other symptoms by 5 years or more, providing a criti cal window for diagnosis and treatment. That's a lot of systems to remember. Basically, think about Whipple's in white middle-aged men with diarrhea, fat malabsorp tion/weight loss, CNS symptoms, and recurring episodes of inflammatory arthritis.

with

aseptic

picture,

arthritis

which

frequently

resolves

with

have

minimal

Parvovirus B19 is one of the more common causes of aseptic synovitis in adults. Think about parvovirus B 19 when you see a young adult female with a history of exposure to school-aged children who presents with symmetric synovitis of the hands (mimicking RA) and macular rash (75%)-the synovitis has been present for weeks, and she may even describe a recent "slapped

macrophages

cheek" rash in the children. Again, the history of expo

containing periodic acid-Schiff (PAS)-positive gram

sure to sick children 1-2 weeks prior to the arthritis

positive bacilli in tissue biopsies from any system that is

should alert you to the possibility of parvo as the cause

The

diagnosis

made

finding

of hand arthritis. The diagnosis can be confirmed by

involved. PCR can also be used. Treatment usually requires parenteral antibiotics (e.g.,

positive IgM against parvovirus B19.

ceftriaxone) initially to ensure CNS penetration, followed

Other causes of aseptic synovitis: rubella, mumps,

by oral therapy, such as double-strength TMP/SMX

acute

x l-2years! Recurrences are common.

with maculopapular rash, fever, and urticaria before

HBV

(oligoarthritis/arthralgias

associated

jaundice), chronic HCV, and enteroviruses.

TUBERCULOUS ARTHRITIS Tuberculous arthritis typically presents as an indolent

LYME ARTHRITIS

chronic monoarthritis (months to years). Hip and knee

Remember endemic areas for Lyme disease include:

joints are most commonly affected. The arthritis is either

the Northeast and North Central states (Minnesota,

an expression of primary TB or a site of reactivation,

Wisconsin), as well as the West Coast, particularly

but most patients do not have associated active pulmo

Northern California. Lyme arthritis is a late manifesta

nary TB. Remember that immunosuppressive agents,

tion of Lyme disease. It occurs a few months, and up to

particularly anti-TNF inhibitors, are risk factors for reactivation TB. Joint fluid may show inflammation (average WBCs

20,000 mononuclear cells/mm3). Know that acid-fast

1- 2 years, after the disease-causing tick bite in 50% of untreated patients. True Lyme arthritis is an intermittent or persistent, asym metric, monoarticular or oligoarticular arthritis, usually

smears and cultures are useful, but their sensitivities

affecting only I or a small number of large joints (knee

are not great. Synovial cultures are positive in

most commonly). Up to 50% of patients never have evi

�

80% of

dence of early Lyme disease (e.g., erythema migrans,

people with infection. As with pleural TB, biopsy of the synovium for pathology and culture is most helpful. (Pathology shows granulomas.)

carditis, cranial nerve abnormalities, peripheral neuropa thies, mononeuritis multiplex, or meningoencephalitis). A small number of patients actually develop destructive, erosive arthritis. (See Infectious Disease, Book 1.)

Send the fluid for TB PCR-the test is very sensitive. A positive TB skin test in a patient with a chronic joint effusion should make you think about (and investigate for) TB! As with pulmonary TB, TB skin tests aren't always positive in people with infection, so do not let a negative test dissuade you from the workup if you suspect TB based on the history or other data.

Criteria

have

been

established

for

diagnosis

and

treatment of Lyme disease by the Infectious Diseases Society of America ([IDSA] initially updated in 2006; reviewed for accuracy in 2011). Diagnose Lyme arthri tis using a serum ELISA test for anti-Borrelia burgdor feri lgG. The lgM ELISA test is not appropriate because arthritis represents a late manifestation (thus, IgG is

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INFECTIOUS ARTHRITIDES

disease," but know that definitive data do not exist to support this claim. Thus, some prefer the term post

uiz •

Lyme syndrome. As such, it is inappropriate to treat any form of Lyme disease with prolonged oral or intravenous

What are presenting features of Whipple disease?

antibiotics. In very rare circumstances, a patient with

The organism involved?

late neurologic involvement may require an additional I month of parenteral ceftriaxone after the I 51 month of

•

Describe the presentation of tuberculous arthritis.

•

How do you diagnose Lyme arthritis?

•

What are the features of adult-onset Still's disease?

treatment, but no patient should receive more than two 28-day parenteral regimens. Multiple months of oral or parenteral antibiotics, and antibiotics that are ineffective against the organism (e.g., azithromycin, tetracycline,

more appropriate), and these lgM tests are often falsely positive. Do not do any further testing if the IgG ELISA

tinidazole, rifampin, atovaquone/proguanil Hcl, arte misia), are not considered standard of care by the JDSA.

test is negative; a negative test excludes Lyme as the cause of arthritis.

LESS COMMON ARTHROPATHIES

False-positive Lyme ELISA serology can be caused by

This section contains joint diseases that are associated

many diseases, including SLE, RA, Rocky Mountain spotted fever, and other spirochetal diseases (syphilis and leptospirosis), and is seen at a high rate in healthy controls. So, order a Western blot as a confirmation test in patients with a +lgG ELISA.

with systemic illness; although they are less commonly seen in clinical practice, they seem to show up on Board exams!

Adult-Onset Still's Disease

Although the test is not readily available commercially, DNA amplification is useful on joint fluid. The rate of false positives is high, so do not order this test unless the patient has a positive IgG ELISA and Western blot. The DNA can persist in the joint long after adequate treatment; hence, a positive P CR test does not identifY whether disease is active or treated. Antibody tests on the joint fluid are not helpful. Lyme arthritis without neurologic involvement should be treated with a course of oral doxycycline or amoxicil lin for 21 days; then reassess.

Adult-onset Still's disease (AOSD) is an uncommon illness that occurs primarily in adults in their 20s to 30s; onset after age 60 is unusual. A similar disorder, called systemic-onset juvenile arthritis, is more com monly seen in children younger than 16 years. AOSD presents with a distinctive "evanescent" (means "van ishing" or "disappearing"), macular, salmon-pink rash that coincides with a daily ("quotidian") high, spiking fever and significant leukocytosis (Yamaguchi criteria). The coincidence of a rash that appears with the fever and disappears at defervescence is a big clue to the diagnosis

P ersistent synovitis after oral antibiotics can be treated with NSAIDs and observation, as occasionally the inflammation of Lyme takes weeks to improve. If the patient still has synovitis after oral antibiotics and a period of observation and NSAIDs, retreatment with another 21 days of oral doxycycline or amoxicillin is appropriate. Ceftriaxone can be used for 14-21 days in patients who do not improve at all after the initial oral

in practice. Include AOSD in the differential diagnosis of fever of unknown origin (FUO). Mild oligoarthritis usually develops in most patients. Joint fluid is inflammatory (average WBCs= 13,000 cellslmm3). Other

signs/symptoms

include

sore

throat,

serositis. Some patients may progress to a destructive polyarthritis, and their joints can actually fuse (espe

regimen.

cially the wrists), but this is not common.

Once Lyme arthritis has been treated with ceftriaxone

Associated lab abnormalities include:

x 21 days, or 2 regimens of oral antibiotics, the patient has been definitively treated, and any further symptoms/

•

rheumatologist. Options include NSAIDs, hydroxychlo

neurologic involvement (except for isolated Bell's palsy) should undergo a lumbar puncture and be considered for treatment with intravenous ceftriaxone, instead of oral antibiotics. Some

patients

•

reactive thrombocytosis, increased ESR or CRP, liver transaminase elevations, and very high serum ferritin levels.

Besides the rash, a high serum ferritin level (> lOx normal) is strongly associated with this disease and correlates with more severe disease activity.

with

persistent

symptoms

that

are

indistinguishable from chronic fatigue syndrome or fibromyalgia receive the diagnosis of "chronic Lyme

•

Know that any patient with Lyme arthritis who has

anemia of chronic inflammation (or anemia of chronic disease),

inflammation should be treated conservatively by a roquine, and intraarticular steroids.

lymph

adenopathy, splenomegaly, myalgias, arthralgias, and

Initial treatment for mild disease includes NSAIDs, but most patients ultimately require systemic steroids. Methotrexate is the most common DMARD used for

6-31

6-32

INFECTIOUS ARTHRITIDES

those with severe disease and as a steroid sparing agent. Biologics with IL-l inhibitors have been shown to be effective, though some patients may respond to anti-TNF therapy. Hemochromatosis Arthritis About 20--40% of patients with hemochromatosis develop arthritis; in many, the arthritis is the presenting symptom. Usually, this happens in patients > 50 years of age. Monthly menstrual cycle acts as a form of phlebot omy, so women with hemochromatosis may not have a manifestation of CPPD until after menopause. Therefore, still consider this diagnosis in postmenopausal women. The arthritis affects small joints first. Think of hemochromatosis when you see synovitis of the 2"d and 3'd MCPs. Larger joints (e.g., knees, ankles, shoulders) are affected later. The joint fluid is noninflammatory (a big clue to help you distinguish this arthritis from the inflammatory ones that also affect the MCPs, such as RA). The morning stiffness of this arthritis is also usu ally < 30 minutes; x-rays show narrowed joint spaces. Remember that CPPD deposition occurs in association with hemochromatosis-in 50% of patients with the arthritis. So, you also may see chondrocalcinosis on radiographs and/or weakly positive birefringent crystals in the joint fluid. -

Treating hemochromatosis with phlebotomy may help other manifestations of disease but not the arthropathy. Treat chronic joint disease with acetaminophen and NSAIDs. Intraarticular steroids and NSAIDs can be used for acute CPPD arthritis flares (see CPPD deposition dis ease, above). Hemochromatosis can easily be screened for with iron studies. An elevated iron saturation level (iron/TIBC of > 45%) or elevated ferritin level (> 200) suggests the diagnosis. Neuropathic Arthropathy (Neuropathic Joints) We used to call these Charcot joints-joints that are destroyed via 2 proposed mechanisms: I) Repeated trauma secondary to loss of pain sensation and/or proprioception 2) Autonomic dysfunction that leads to regional hyperemia, osteoclastic stimulation, and active bone resorption Diabetes mellitus is the most common cause. Joint findings are similar to severe OA, with osteophytes, except that erosions also can occur. The metatarsophalangeal, tarsal, and talar joints are most commonly involved and radiographs confirm the diag nosis. Bony fragments, reminiscent of the trauma, are often seen floating in the joints on radiographs. To try to repair the damage, bone becomes overgrown, known

as periost1t1s, and noninflammatory joint effusions develop. Eventually, the joints become unstable and lax. Think about this diagnosis in a diabetic patient with a horrific-looking joint (especially the foot) and minimal associated pain. Treat joints with stabilization and focus on the underlying disease. Hypertrophic Pulmonary Osteoarthropathy Think about hypertrophic pulmonary osteoarthropathy (HPOA) when you see polyarthritis/joint effusion in a smoker who also has clubbing of the fingers. HPOA can be primary or familial, but it is most often associated with lung malignancies (termed "secondary HPOA"). We don't know the mechanism for this condition, but it is associated with periosteal bone formation, joint effu sions (due to synovial proliferation and inflammation), and clubbing (due to effects on connective tissue). The bone changes can be associated with dull, aching pain that is intense when you apply pressure to the arms and legs. The arthropathy is usually slight and appears noninflammatory (effusion WBCs < 500 cells/mm3). Hands are generally not part of this presentation, other than clubbing! In early stages, radiographs show periosteal bone growth adjacent to radiolucencies, especially in the diaphysis. Later, irregular cortical thickening appears, mostly over metaphyses. Use imaging to look for an intrathoracic malignancy, especially lung cancer. Infectious etiologies are also seen in this syndrome, including bronchiectasis, lung abscess, and TB. If the cause is a lung infection, the arthropathy and clubbing usually disappear after antibiotics. Remember: Think HPOA in the patient with polyarthritis (similar to RA), clubbing of the fingers and toes, and periostitis of the long bones. When you see this triad, evaluate the patient for lung cancer. Post-Streptococcal Reactive Arthritis Post-streptococcal reactive arthritis (PSRA) is considered a separate entity from acute rheumatic fever (ARF) and from typical HLA-B27-associated reac tive arthritis. Onset of PSRA is within I 0 days of group A streptococcal infection; patients may present with prolonged or recurrent arthritis that is additive (rather than migratory). There is a bimodal distribution: child hood and middle age; incidence of developing carditis is low. There is little consensus on treatment, but aspirin, NSAIDs, and steroids have been used. The role of antibiotics is controversial.

OTHER CONNECTIVE TISSUE DISEASES

changes; digits may tum white, then flush red without becoming blue. If rewarming and vasodilation do not occur, the digits can become necrotic. P aresthesias, pain, and clumsiness may be associated with the vasospastic •

•

Does hemochromatosis initially affect large or

episode. Fingertip ulcerations are an indicator of asso

small joints?

ciated rheumatologic disease, because ulcerations rarely

Characterize the typical patient who develops

The following suggest secondary Raynaud phenomenon:

primary Raynaud's. •

occur in primary Raynaud phenomenon.

Mixed connective tissue disease has features of which diseases?

male, age

30, asymmetry of findings, fingertip ulcer

ations, and coexistent vascular or autoimmune disease. An easy test to distinguish primary from secondary

OTHER CONNECTIVE TISSUE DISEASES

based lubricant over the nail beds and examine them with an ophthalmoscope. Abnormal, dilated, and tortu

RAYNAUD PHENOMENON

ous capillaries at the nail bed are highly indicative of a

Primary Raynaud phenomenon (idiopathic; called Raynaud disease) usually begins in young women within a few years following menarche and is not associated with any rheumatologic disease. In

Raynaud's is nailfold capillaroscopy. Apply clear water

�

90% of young

women with Raynaud phenomenon, the condition is primary (i.e., the disease) and without any significant sequelae. Raynaud disease can cause livedo reticularis.

microvascular abnormality seen in rheumatic diseases. Nailfold capillaroscopy is the diagnostic test of choice to confirm suspicion of secondary Raynaud phenomenon in an autoimmune disease! Treatment includes avoiding the cold and drugs that cause vasoconstriction. Smoking/ tobacco use is contraindicated. Treatment includes: cal cium channel blockers, alpha-blockers, sildenafil, and nitroglycerin transdermal. Localized

digital

sympa

Secondary Raynaud phenomenon is typically more

thectomy should be limited to patients who have failed

severe and occurs in association with connective tissue

medical treatment and who continue to experience isch

diseases and with certain prescription and illegal drugs. It

emia or are at risk of losing a digit. When stress triggers

is present in most scleroderma patients, but also is seen

Raynaud's, relaxation techniques may be helpful.

frequently in RA, SLE, Sjogren's, mixed connective tissue disease (MCTD), primary biliary cirrhosis (P BC), and dermatomyositis. Common drugs that may exacer bate Raynaud's include: •

•

Acrocyanosis may be confused with Raynaud's. It is distinguished by

persistent

blue/cyanotic fingertips/

toes and the absence of pain. Thromboangiitis obliter ans (TAO, a.k.a. Buerger disease) may also resemble

Serotonin agonists (e.g., trip tans, beta-blockers,

Raynaud's. TAO is a vasculitis characterized by recur

ergots)

ring progressive inflammation and thrombosis of small

Chemotherapeutic agents (e.g., bleomycin,

and medium arteries and veins of the hands and feet in

vinblastine, cisplatin)

association with tobacco use. Claudication and ischemia

Sympathomimetics (e.g., decongestants, clonidine, cocaine, and methamphetamines)

with digital necrosis are common. Smoking cessation is the mainstay of treatment.

Smoking decreases digital blood flow and must be avoided.

MIXED CONNECTIVE TISSUE DISEASE

Raynaud phenomenon is defined and manifested as a

These patients have signs of several diseases, including

sequential, tricolor change of the fingers and/or toes that occurs as a result of vasoconstriction with exposure to cold or emotional stress--even the stress of going to the doctor can elicit the response in some patients (Image

6-13). Fingers and/or toes blanch or tum white

(as a result of vasoconstriction); when cyanosis due to decreased occurs,

oxygenation

the

digits

upon

tum

-->

blue

approaching

red).

classic

not

have

triphasic

MCTD usually does not have antibodies against dsDNA, uncommon.

the

color

Only rarely do these patients get heart failure from Image 6-13: Raynaud syndrome

100%, so a negative result essentially rules

Smith, SS A (Ro), or SSB (La) and renal involvement is

Raynaud's even though do

(9: 1).

out MCTD. Although SLE may also have anti-Ul-RNP,

A patient may still have they

lung disease may be the most severe complication.

titers are associated with MCTD, and it has a sensitivity

rewarm -->

tis and/or serositis, as well as "swollen hands." Interstitial

Anti-U1-RNP is the autoantibody to remember: High

ing, the digits flush red (white

typically presents with arthritis/arthralgias and Raynaud phenomenon. The patient may present with a mild myosi

This disorder predominantly affects women

blue; finally, with vaso dilation

SLE, polymyositis, and systemic sclerosis-but mixed together. Mixed connective tissue disease (MCTD)

myocarditis or severe pulmonary hypertension.

6-33

6-34

ANTIPHOSPHOLIPID SYNDROME

lgG4 RELATED DISEASES

Because other conditions can be transiently associated

These are typically seen in middle aged and older males. They are caused by infiltrative disease of IgG4-positive plasma cells with fibrosis. Presentation may include a

localized

mass,

retroperitoneal

fibrosis,

autoim

mune pancreatitis, sclerosing sialadenitis, and aortitis. Symptoms can mimic malignancies, infections, and autoimmune diseases. Diagnose with elevated serum lgG4 level and biopsy of affected organs. Treat with prednisone and DMARDs (rituximab). There may be a risk for malignancy in these patients.

with AP antibodies, but not the syndrome, the antibodies must be present on 2 separate occasions at least 12 weeks apart for diagnosis of APS. While not included as criteria for diagnosis, other findings seen with APS include: •

Livedo reticularis (Image 6-14)

•

Sterile cardiac vegetations (Libman-Sacks endocarditis)

•

Thrombocytopenia

•

Prolongation of the partial thromboplastin time (PTT) caused by LAC. (Mixing studies are done on plasma to differentiate factor deficiency from factor inhibi tor. In a mixing study, the patient's plasma is mixed 50:50 with normal plasma. If the patient's prolonged

ANTIPHOSPHOLIPID SYNDROME Antiphospholipid syndrome (APS) can

PTT is due to factor deficiency, the mixing with

be primary

and idiopathic, or it can be secondary and associated with another disease (usually SLE), drugs, or an infec tion. APS is characterized by the presence of I or more antiphospholipid antibodies along with the following findings of either vascular thrombosis or pregnancy One or more of the antiphospholipid (AP) antibodies: Lupus anticoagulant (LAC)

Anticardiolipin antibodies (lgG or lgM in medium/ high titer) Anti-13,-glycoprotein I antibodies (lgG or lgM at any titer)

Patients with APS are physiologically hypercoagulable, from a laboratory standpoint! the most pathogenic. Patients with elevated levels of these APL antibodies, but without clots and/or fetal wastage syndrome, are treated prophylactically with ASA 81 mg daily. mortality and manifests as multiorgan dysfunction sec

Vascular thrombosis: venous (e.g., deep venous

ondary to numerous thromboses. Treatment includes

thrombosis and/or pulmonary embolism) and/or

anticoagulation, glucocorticoids, and plasma exchange.

arterial clots (e.g., stroke, myocardial infarction) •

factor inhibitor.)

Catastrophic APS is a rare variant that carries a 50%

Plus either of the following: •

then again prolongs after the mixing study, then the coagulopathy is most likely secondary to a clotting

LAC and anticardiolipin IgG antibodies tend to be

correct the problem. If the PTT initially corrects and

despite appearing to be "anticoagulated" (elevated PTT)

morbidity: •

normal plasma will provide the missing factor and

Acute treatment of APS: Acute clots are treated with

Pregnancy morbidity presenting as: o

Miscarriage of a normal fetus at

anticoagulation, usually low-molecular-weight heparin (LMWH).

2: I 0-weeks gestation

Chronic treatment of APS: Treat the underlying disease

Birth of I or more premature babies

if APS is secondary. Anticoagulation is usually given.

at < 34-weeks gestation because of eclampsia/

Lifelong anticoagulation is used to treat primary disease.

preeclampsia/placental insufficiency o

Multiple miscarriages

(2: 3) at< I 0-weeks gestation

Warfarin is given to maintain the INR 2.0-3.0. The addition of hydroxychloroquine has been shown to be beneficial as well; the drug has antithrombotic effects. Patients with a history of pregnancy-related morbidity should receive prophylaxis for subsequent pregnancies with LMWH and ASA 81 mg. Warfarin should not be given because it is teratogenic.

SJOGREN SYNDROME Sjogren

syndrome

caused

CD4+

T-cell

lymphocytic infiltrate that destroys the exocrine glands (lacrimal and salivary glands), resulting in decreased secretions from these glands.

Image 6-14: Livedo reticularis

SYSTEMIC SCLEROSIS I SCLERODERMA

and muscarinic agonists (pilocarpine and cevimeline) may be helpful for xerostomia symptoms, but have

Qw.dQuiz •

limited efficacy for xerophthalmia.

What are the features of antiphospholipid syndrome?

•

Sjogren patients are at increased risk for

OVERVIEW

developing what other disease? •

Systemic sclerosis was formerly known as scleroderma.

Which autoantibodies are associated with diffuse

Scleroderma is the term used to describe shiny, hard,

SSe? What complication are the antibodies

thickened skin. Morphea is when sclerosis is isolated

associated with? •

SYSTEMIC SCLEROSIS I SCLERODERMA

or localized to a small cutaneous area, but when the

What are the key features of limited SSe?

sclerosis is widespread with the potential for involving internal organs, it is called "systemic sclerosis" (SSe).

Primary

Sjogren

disease

(not

associated

with

concurrent rheumatologic disease) occurs commonly in middle-aged women (F:M, 9:1) who present with sicca complex (dry eyes and dry mouth) along with parotitis and adenopathy. Some patients have subacute cutane ous lupus erythematosus ([SCLE]; see SLE: Skin and Mucous Membranes on page 6-14 ), purpura, and inter stitial nephritis (with Type I [distal] RTA). These patient findings resemble SLE clinically, but not serologically. 70% are RF+, and 20% are ANA-. 65% are SSA (Ro)+, and 50% are SSB (La)+. Note: SSA antigen may be

We will focus on SSe. SSe can be diffuse or limited in its expression depend ing on the extent of skin involvement. The general rule of thumb: If skin is involved above the elbow and the knee (approaching or involving the torso), diffuse SSe is present; if skin involvement starts at the fingertips and extends up to the elbow or from the toes to the knee), then limited SSe is present. The face can be involved in both diffuse and limited SSe. ANA is positive in 2:95% of those with SSe.

present without SSB; however, it is rare to find SSB antigen alone without also having SSA.

TYPES OF SYSTEMIC SCLEROSIS

Secondary Sjogren syndrome can occur with any of the

connective tissue diseases

(RA,

SLE, polymyositis, and

Diffuse SSe(- 20%)

systemic sclerosis) and can be associated with the same

Diffuse SSe (dcSSc) causes diffuse skin thickening

autoantibodies. There is an association with DR3 (as seen

and is more likely than limited SSe to have multiorgan

in SLE and occasionally in polymyositis). There is up to a

involvement. 30% of patients with dcSSc have anti

40-fold increased risk of B-cell

lymphoma with Sjogren syndrome! Follow patients for persistent lymphadenopathy. Close attention to dental care is paramount because these patients are at high risk for dental caries and extractions due to the sicca symptoms: xerostomia (dry mouth), xerophthalmia (dry eyes). Also, remember that children born to mothers with anti-Ro and anti-La antibodies (especially anti-Ro) are at risk for congenital heart block and neonatal lupus (can present as a SCLE rash in a newborn). To diagnose Sjogren's: Assess history for xerostomia and

xerophthalmia;

check

for

autoantibodies;

and

Scl-70

(antitopoisomerase I) antibody-positive. The

antibody is associated with development of interstitial lung disease and reduced survival. The other antibody associated with dcSSc is anti-RNA polymerase III. It is associated with a much higher risk of scleroderma renal crisis, but a lower risk of interstitial lung disease when compared to those with anti-Scl-70 antibodies. Diffuse SSe has a wide range of presentations based on what organs are affected. Scleroderma renal crisis (SRC) is a medical emergency and almost exclusively occurs in dcSSc.

perform a biopsy of minor salivary glands to confirm the

Limited SSe(- 80%)

diagnosis. Xerophthalmia is diagnosed with a positive

Limited SSe (lcSSc) causes skin thickening distal to the

Schirmer test:

5 mm of wetting in 5 minutes (normal

elbows and knees and can affect the face and neck. It

result is� 15 mm).

affects the internal organs to varying degrees. Limited

Treatment of Sjogren syndrome is symptomatic: wetting

SSe may also be referred to as CREST syndrome. Its

agents, pilocarpine tablets, and puncta! plugs for the eyes. Corticosteroids and other immunosuppressants do not improve the sicca symptoms in patients with Sjogren's, so use is reserved for patients who have

key features are well described by the acronym CREST so you can still use it as a mnemonic: •

•

extraglandular disease; e.g., peripheral neuropathy or lupus-like features. Antimalarial agents can help with arthralgias, fatigue, and rashes. Parasympathomimetic

•

Calcinosis (Image 6-15) Raynaud phenomenon (secondary; see page 6-33) Esophageal dysmotility Sclerodactyly Telangiectasias (mucosal; Image 6-16)

6-35

6-36

SYSTEMIC SCLEROSIS I SCLERODERMA

Not

all

features

CREST

need

present.

Anti-centromere antibody (ACA) is specific for lcSSc

nailfold capillaroscopy can be used in this setting to detect abnormal microvasculature in these patients.

and is seen in about 50% of patients. Pulmonary hyper tension can occur in limited scleroderma (10%), while interstitial lung disease usually does not (good candidate for an exam question). Patients who are ACA+ tend to

SSe: Joints Patients with SSe can have a mild, symmetric (like

develop more severe digital ischemia and pulmonary

RA and SLE) hand stiffness +/- synovitis, but it rarely

hypertension.

involves the hand joints (unlike RA and SLE). Patients with dcSSc can have a tendon friction rub, such as at the elbow, which is considered pathognomonic for SSe.

Systemic Sclerosis Sine Scleroderma This form of systemic sclerosis affects about I% of patients. It is characterized by visceral disease without

SSe: Muscles Patients have mild muscle pain and weakness along with

skin involvement.

mild CPK elevations. Occasionally, there are features similar to polymyositis ("overlap syndrome"�r, the

MANIFESTATIONS OF SSe

mild CPK elevation may be due to muscle atrophy from disuse, secondary to skin tightness.

SSe: Skin Skin changes follow a progression of mucinous edema, then induration, and finally fibrosis and atrophy.

SSe: Lungs

Limited SSe typically involves the distal extremities

Lung disease is the main cause of morbidity and

and face.

mortality in SSe. Cause of lung death in SSe is often

Raynaud's eventually occurs in almost all patients with both limited and diffuse types of SSe, and severe vaso

pulmonary hypertension from l of2 causes:

I) Pulmonary arterial hypertension: intimal proliferation

constriction can be associated with digital tip ulcerations,

without interstitial or alveolar inflammation (espe

osteomyelitis, and black fingertips. Acroosteolysis sub

cially in anti-centromere+, lcSSc)

sequently develops. In lcSSc, Raynaud's usually occurs first-several years before other manifestations, but in dcSSc, Raynaud's commonly occurs at the time of other manifestations. See page

6-33 for a more extensive

discussion on Raynaud's. Telangiectasias (the T in CREST) occur in dcSSc but are much more likely in lcSSc (Image

6-16).

Diffuse SSe skin changes characteristically involve entire extremities, chest, abdomen, and face.

2) Interstitial

fibrosis

secondary

alveolitis

and

pulmonary fibrosis Order pulmonary function tests (PFTs) with spirometry regularly (every 6-12 months) to monitor for pulmonary involvement. A decreased DLCO may be the l" sign of pulmonary hypertension. Cyclophosphamide may be used for interstitial lung disease with active alveolitis. Pulmonary hypertension is often treated with drugs that cause vasodilation of the

Sclerodactyly is the term used to describe localized

pulmonary vasculature such as prostaglandins, bosentan,

scleroderma of the fingers or toes (either type).

sildenafil, and/or inhaled iloprost.

Abnormal nailfold capillaries may occur in either type

Lung transplant is occasionally a viable option for

of SSe. These capillaries are reduced in number, while

scleroderma patients with lung disease.

the remaining enlarged capillaries form visible giant loops. These are important because there is a direct correlation between degree of abnormality of the nail

Patients are at increased risk for lung cancers, especially if they smoke.

fold capillaries and severity of the SSe. Remember, the

Image 6-15: Calcinosis of the .fingertips

Image 6-16: Telangiectasia

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SYSTEMIC SCLEROSIS I SCLERODERMA

have reperfusion defects on thallium stress tests, but true

Q •

coronary artery disease is frequently absent. The abnormal

uiz

stress result is presumed to be due to episodic vasospasm. Diastolic dysfunction is common.

Abnormal nailfold capillaries are more commonly seen in which autoimmune disease?

•

What lung manifestation is often the cause of death in patients with diffuse SSe? With limited SSe?

TREATMENT Treatment is generally symptomatic and organ-specific, as reviewed above. No medicines change the course of scleroderma.

SSe: Kidney Diffuse SSe only: Before ACE inhibitors, scleroderma renal crisis was the major cause of morbidity and mor tality. Renal crisis presents within the first

5 years of

Localized skin disease can be treated with ultraviolet light therapy. For patients with systemic sclerosis, cyclophosphamide

diffuse disease and is associated with prior or current

is now being used in patients with diffuse disease and

glucocorticoid use and anti-RNA polymerase III anti

early pulmonary involvement.

bodies. Patients develop acute malignant hypertension and renal failure with an active urine sediment. Always consider the diagnosis of dcSSc in a young female who presents with acute malignant hypertension and renal failure. Patients may even present with thrombocytopenia and microangiopathic hemolytic anemia

(MAHA), which

Patients suspected of pulmonary hypertension should be evaluated with an echocardiogram. Have a low threshold to evaluate the patient for TLD with a high resolution CT scan and/or PFTs, especially in those with antitopoisom erase I (anti-Scl-70) antibody positivity. Steroids and an immunosuppressant usually are given to treat alveolitis.

mimics thrombotic thrombocytopenic purpura (TIP).

Bosentan, sildenafil, or the prostacyclin analogs (e.g.,

ACE inhibitors are started early and are useful even if

epoprostenol) are options for pulmonary hypertension.

overt renal failure develops-because renal failure may

Some patients require a lung transplantation.

be reversed with their use.

Patients with diffuse disease should monitor their blood pressure monthly. Every

SSe: Gl Diffuse

3 months, check the urine

protein:creatinine ratio and estimate the glomerular SSe

only:

Wide-mouthed

diverticula

are

pathognomonic of dcSSc, but not lcSSc. Limited SSe only:

associated with

filtration rate (GFR). Proteinuria and a> 20% reduction in GFR predicts renal crisis. Prescription for an ACEI or ARB should be given as soon as the blood pressure

primary biliary

cirrhosis (PBC) and positive anti-mitochondrial antibody. Both dcSSc and lcSSc: Dysmotility throughout the GI tract, but especially the esophagus (the E in CREST) and the stomach (gastroparesis) are problematic for patients with lcSSc or dcSSc. Also, as the disease progresses, the

changes so as to prevent renal crisis. Also, remember that corticosteroids have little to no efficacy in SSe and are associated with the development of renal crisis, so they should be avoided in most circumstances (except alveolitis). Limited SSe has a better prognosis than diffuse. But

lower esophageal sphincter relaxes, so patients develop

remember that these patients can get pulmonary hyper

severe GERD with a propensity for chronic esophagitis,

tension (especially those anti-centromere Ab+), and

strictures, and Barrett disease. Proton pump inhibitors

severely

are used in symptomatic patients. Prokinetic agents, like

associated with increased mortality.

erythromycin, may also be helpful. Mucosal telangiectasias may be present throughout the G I

elevated

pulmonary

arterial

pressures

Diffuse SSe usually progresses within the first

are

5 years,

after which no new organ systems are affected (although

tract. Telangiectasias in the stomach can lead to bleeding

the organ systems that were initially affected continue

and iron-deficiency anemia. This syndrome is called

to deteriorate). After this first explosion of disease, the

gastric antral vascular ectasia (GAVE) or "watermelon

skin usually begins to atrophy and loosen up, except for

stomach" because of its endoscopic appearance.

the hands. Know that the extent of skin disease in dcSSc

Dysphagia, constipation, intestinal pseudoobstruction, and malabsorption are also seen in both dcSSc and lcSSc.

SSe: Heart Cardiac involvement is common in SSe, and symptomatic disease portends a poor prognosis. Heart findings include cor pulmonale, restrictive pericardia! disease, and con duction defects/arrhythmias. The majority of patients

is a marker for the severity of visceral disease. If renal crisis is going to happen, it typically occurs within the first

5 years of disease. Blood pressure elevations signal

impeding renal disease and eventual renal crisis if not controlled.

6-37

6-38

EOSINOPHILIC FASCIITIS

Polymyositis

E OSINOP HILIC FASCIITIS

Features of polymyositis (PM) may be found in patients Eosinophilic fasciitis (EF) causes both scleroderma-like

with other autoimmune disorders, such as SLE and

and nonscleroderma-like skin changes in the extremities

MCTD. It is occasionally associated with the MHC

often sparing the hands (typically without Raynaud's,

Class II HLA antigen DR3.

and without SSe-associated antibodies, including ANA). EF can follow unaccustomed rigorous exercise or be paraneoplastic (e.g., lymphoma, myeloma). Tender,

migrating

edema

the

PM manifests as symmetric proximal muscle weakness and, in some patients, mild myalgias. PM (and der matomyositis) typically does not cause neuropathy,

only myopathy. Weakness usually occurs first in the

polyarthritis of the hands may be present in some

extremities

proximal muscles (hips and thighs > shoulders and arms)

patients.

and mimics muscular dystrophy. These patients may

So, 3 useful clues to help you distinguish this SSe mimic from SSe are:

present with difficulty rising from a squatting or kneel ing position. Remember: Myositis generally presents with weakness, not pain! This is an important feature in

1) Negative ANA

distinguishing myositis from polymyalgia rheumatica,

2) Absence of Raynaud phenomenon

which presents primarily as muscle pain and not a myop athy. Further, CK is high in myositis, while in PMR the

3) Symptoms with preceding vigorous exercise

ESR and CRP is high but CK is normal. Know how to

Nailfold capillaries are normal, and systemic symptoms

distinguish between these two entities! Also know how

are

to distinguish both of these diseases from fibromyalgia.

unusual.

The

nonscleroderma-like

skin

changes

include peau d'orange-type induration (a late feature due to thickening and tethering of the fascial layers), which often occurs on the proximal forearms and upper legs but not the distal extremities. The affected areas have a characteristic "woody" consistency on palpation. Also

unlike SSe,

most patients

As PM progresses, dysphagia (from tongue, pharynx, and

upper

dyspnea

diaphragm

dysfunction), weakness),

dysphonia, and

cardiac/

ECG changes (from myocarditis or CAD) can occur, which

have a peripheral

esophageal

(from may

require

hospitalization

and

aggressive

immunosuppressive therapy.

eosinophilia, which appears early in the disease course, and an increased sedimentation rate. A full-thickness excisional skin biopsy shows an eosinophilic infiltrate

Dermatomyositis Dermatomyositis (DM) is similar to PM in terms of

and fibrosis of the subcutaneous fascia. Eosinophilic fasciitis is occasionally self-limited, but most patients require moderate-dose corticosteroids

(40 mg/day) or steroid-sparing agents (MTX).

weakness, but skin involvement also occurs. In some patients, the skin manifestations may be quite severe or even the sole area of involvement (amyopathic dermatomyositis). Skin changes in DM: consist of a moderate-to-deep, purple-red, papular, sometimes scaly, photosensitive

INF LAMMATORY MYOPATHIES

rash that occurs on the face, neck ("V sign" or "shawl

P OLYMYOSITIS AND DERMATOMYOSI TIS

associated periorbital edema with a heliotrope rash

Overview Inflammatory

sign"), and extensor surfaces of the joints. There is an (Image

diseases

skeletal

muscle

include

6-17). This rash is violaceous and classically

appears on the upper eyelids, but it also may appear on

dermatomyositis and polymyositis (about equal occur

the cheeks and forehead. (SLE's butterfly rash does not

rence), as well as some less-common disorders, such

involve the eyelids.) Gottron papules are flat-surfaced,

1975, Bohan and Peter

reddish-to-violet, scaling papules on the knuckles (these

as inclusion body myositis. In

divided myositis into the following classification, which

actually look more like "cigarette-paper" crinkling of

is commonly used today:

the skin over the MCPs), and these are the most spe cific indication of DM (Image

1) Polymyositis ([PM]; adult)

6-18). Vasculitic lesions

can also develop, more commonly on the extremities.

2) Dermatomyositis ([DM]; adult)

A psoriatic-like rash can appear on the scalp. The scalp

3) Myositis associated with malignancy

4) Childhood polymyositis or dermatomyositis 5) Myositis associated with connective tissue disease (SLE, SSe, MCTD)

Image 6-17: Heliotrope rash

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INFLAMMATORY MYOPATHIES

DM, but another connective tissue disorder (e.g., SSe, SLE, MCTD, or overlap syndrome). Know

uiz •

•

other myositis specific antibodies because they are associated with characteristic phenotypes.

Compare and contrast polymyositis and dermatomyositis.

•Anti-Jo-1: strongly associated with ILD and the

Which autoantibodies are associated with poly- and dermatomyositis?

•Anti-Mi-2: classic DM with V sign and shawl sign.

"antisynthetase" syndrome described above. Mild weakness and very good response to therapy. •Anti-SRP (signal recognition protein): very acute

will be very itchy-this is one of the main complaints of patients! Changes in nail bed capillaries, as discussed under Raynaud's, can be seen in DM (also seen with

Cancer in PM and OM

Antisynthetase Syndrome Antisynthetase syndrome is a specific presentation of PM or DM that is characterized by very acute onset of disease, fevers, and weight loss, Raynaud phenom enon, cracking and discoloration of the hands (termed hands"),

•Anti-p 155/p140: strongly associated with cancer-associated DM.

scleroderma and SLE).

"mechanic's

severe PM and cardiac involvement; poor response to immunosuppression.

polyarticular

and

nonerosive

arthritis, and a predilection for interstitial lung disease. Anti-Jo-1 antibodies (a type of antisynthetase antibody) are often found with this presentation. Interstitial lung disease often is more significant than the myositis. The disease is typically refractory to treatment. Another myositis specific autoantibody is the anti-SRP (signal recognition particle) antibody. These patients have PM and often develop cardiomyopathy. Prognosis

Cancer is present in adults in 7-10% of PM and 15-20% of DM patients at the time of, or soon after, diagnosis of the muscle disease. There is no increased cancer risk in juvenile dermatomyositis. The risk increases with age, up to - 30--40% in patients

65 years of age. The

patient with cancer is usually older than 50 years and has

dem1atomyositis

often

than

polymyositis.

Remember that cancer is most strongly associated with DM, especially in those who are positive for anti-p 155/ p 140, where the risk of cancer approaches 70%. Every patient who is newly diagnosed with either PM or DM must be evaluated for underlying malignancy with age appropriate cancer screening, unless something in the H&P suggests a specific cancer or a location to image.

is poor.

Risk for cancer is highest within the first 5 years of diag

Diagnosis of PM and OM

CT as a screen for cancer in newly diagnosed PM/DM.

nosis. Current data do not support routine total body PET/

PM and DM peak between 30 and 50 years of age. The following findings help establish the diagnosis of PM

The most common associated malignancies are ovarian, lung, pancreatic, colon, and lymphoma.

and DM: •In 95% of patients, increased CPK with numbers in the thousands (not hundreds); you also may see an increase in other muscle enzymes, such as aldolase, LDH, AST, and ALT. •Abnormal, myopathic electromyogram (EMG) (increased fibrillations, decreased amplitude, and spontaneous repetitive activity) with early recruitment. •Abnormal muscle biopsy (gold standard); increase the yield on biopsy by targeting an involved muscle, or by using MRI to select an optimal site. Avoid biopsy of sites recently studied by EMG; instead use the contralateral side. •Skin biopsy in DM: Biopsy of the Gottron papules or erythroderma associated with the shawl sign; may make diagnosis and avoid need for muscle biopsy. Light microscopy and immunofluorescence show abnonnalities at dermal-epidermal junction. •ANA are present in about 60% of patients. The presence of other autoantibodies (anti-Ro, -La, -Sm, -RNP) suggest that the diagnosis is not PM or

MedStudy

Image 6-18: Go/Iron papules

6-39

6-40

NONARTICULAR RHEUMATISM

Treatment of PM and DM

COLCHICINE MYOPATHY I NEUROPATHY

Polymyositis and dermatomyositis are typically treated

Colchicine myopathy/neuropathy mimics polymyositis

with a high-dose prednisone that is slowly tapered while

with proximal muscle weakness, paraesthesias, and

a steroid sparing agent is added (e.g., azathioprine or

elevated CPK. Suspect this in the gout patient with

methotrexate). 80% begin to respond to the steroid within a few days to 6 weeks. Patients

with

renal insufficiency who is taking long-term colchi cine. But remember, PM and DM cause myopathy, not

life-threatening

manifestations

usually

neuropathy.

receive intravenous pulse glucocorticoids. Antimalarials, such as hydroxychloroquine, are helpful for the rash in dermatomyositis. IV immunoglobulin (IVIG) may be effective in patients who do not respond to the other medications. Recent trials with rituximab for the treatment of myositis have been disappointing. Every

adult

patient

should

have

cancer

screening

performed; if there is a poor response to treatment, reassess for cancer!

such as ethanol, cocaine, and heroin are also causes. Statins, especially when combined with gemfibrozil, a fibrate, are a known cause of drug-induced myopathy. Patients may present with myalgias and normal CPK occur. Depending on severity, patients may have weak ness of the proximal muscles as well. If the myopathy is

Remember to prescribe vitamin D, calcium, and

severe (weakness, CPK elevations> 3x normal, or myo

bisphosphonate therapy for those on chronic

globinuria), stop the drugs. Usually, the patients improve

glucocorticoids (all patients, not just those with

when the drug is stopped.

PM/DM). •

Lipid-lowering drugs and chronic corticosteroids are the most common drugs that cause myopathy. Illicit drugs

levels; severe muscle pain and rhabdomyolysis also can

Important points on steroid use: •

DRUG-INDUCED MYOPATHY

Glucocorticoid myopathy typically presents in one of

Think about superimposed steroid myopathy in a

two ways:

patient with PM/DM who initially improves with glucocorticoids but then develops progressive

I) Chronic myopathy:

weakness despite improvement in CPK levels. Treatment is to taper glucocorticoids gradually to avoid a flare in the disease.

•

Chronic use of prednisone � 30 mg/day

•

Proximal muscle weakness

•

Normal CPK and EMG

2) Acute quadriplegic myopathy:

INCLUSION BODY MYOSITIS Inclusion body myositis (IBM) is the most common

•

High-dose IV steroids

inflammatory myopathy in persons > 50 years of age,

•

Severe generalized weakness

and it occurs more commonly in Caucasian men.

•

Elevated CPK +/- myoglobinuria; abnormal EMG

•

Most commonly associated with concurrent use of

IBM is a more indolent disorder characterized by prominent asymmetric distal weakness (buzz words =

weak handshake), although proximal weakness is

common, especially affecting the quadriceps. Dysphagia is often a prominent symptom and can lead to aspiration pneumoma. History should focus on possible drug exposures (e.g., antimalarials,

glucocorticoids,

colchicine,

neuromuscular blocking agents in critically ill patients Consider the acute form as a possible cause of diaphragm weakness in patients who are difficult to wean from the ventilator. Glucocorticoid myopathy is an exclusionary diagnosis; patients improve when you stop the drugs and start physical rehab.

statins,

cocaine) and alcohol use.

NONARTICULAR RHEUMATISM

No lab studies are helpful except for muscle biopsy! CPK may be only mildly elevated. Markers of inflam

FIBROMYALGIA

mation are absent, and no autoantibodies are developed.

Fibromyalgia

Diagnosis is made by a suggestive history in combination

characterized by hyperalgesia. This noninflammatory

(FM) is a hypersensitivity syndrome

with a muscle biopsy showing vacuoles and filamentous

disorder has been associated with neurochemical imbal

inclusions.

ances that result in increased sensitivity and heightened

Take patients off the precipitating drugs and give a trial of steroids. Unlike PM/DM, inclusion body myositis is only minimally responsive to treatment.

response to painful stimuli. More women are affected than men, estimated female:male ratio is

I 0: I. Patients

often complain of diffuse myalgias, ali-day stiffness, excessive fatigue, and nonrestorative sleep. The previous American

College

Rheumatology

(ACR) criteria relied heavily on finding "tender points"

NONARTICULAR RHEUMATISM

Pharmacologic interventions include: antidepressants or combination of antidepressants (low-dose tricyclics +/ SSRis or reuptake inhibitors), antiepileptics, and/or non narcotic analgesics). Steroids and NSAIDs are useful •

•

only for coexisting inflammatory conditions. Opioids

Which drugs cause myopathy?

should be avoided because they have limited efficacy

Which drugs are used to treat fibromyalgia?

on exam. In

and significant risks.

20 I 0, the ACR released new criteria for

fibromyalgia based on a quantitative measure of wide spread pain (in lieu of a tender point exam) using:

I) the widespread pain index (WPI: 0-19), and 2) the symptom severity (SS) scale (0-12), which is composed of 4 variables: degree of fatigue, waking unrefreshed, cognitive impairment, and general somatic symptoms.

Tramadol has been shown to be effective, possibly because the drug has an SSRI-like effect. In general, do not prescribe narcotics for FM patients.

Tricyclic antidepressants (TCAs) increase the duration of stage 4 sleep, which has been found to be decreased in these patients. Cyclobenzaprine has a chemical structure similar to TCAs and is also commonly used. In studies, deprivation of stage

4 sleep causes many otherwise

healthy people to get the symptoms of fibromyalgia!

Significant impairment, consistent with a diagnosis of

Whether there is a causal connection is uncertain.

Duloxetine and milnacipran are FDA-approved "dual

FM, is defined as: •

WPI> 7 and SS> 5, or

•

WPI

reuptake inhibitors" that block reuptake of both sero tonin and norepinephrine. Adding an SSRI or a reuptake

3-6 and SS> 9.

inhibitor to a tricyclic is sometimes used in patients who

Symptoms must be present at a similar level for

complain of fatigue or exhaustion coupled with mood

2:: 3 months, with pain above and below the waist; all

disturbances. Be aware that this combination increases

other causes of similar symptoms must be excluded first.

the risk of serotonin syndrome. Note that combining

Understand that other entities (e.g., obstructive sleep

tramadol with an SSRI increases the risk for serotonin

apnea,

syndrome.

hypothyroidism)

can

cause

symptomatology

similar to fibromyalgia and that fibromyalgia can coexist with other diseases.

Pregabalin (antiepileptic) is the 151 medication FDA approved specifically for fibromyalgia, but gabapentin,

Consider the following labs to evaluate for other

which is less expensive, is a frequently used and effec

disorders: ESR, TSH, CPK, CBC, and liver transami

tive off-label treatment. Both alleviate the pain.

nases. A sleep study may be needed to reveal sleep apnea or another cause of excessive daytime somnolence. Patients

with

fibromyalgia

often

have

There may be an increased incidence of suicidal thoughts in patients taking pregabalin, duloxetine, or milnacipran.

associated

disorders including: depression/anxiety, stress, history of emotional and/or physical trauma (e.g., sexual abuse),

MYOFASCIAL PAIN SYNDROME

migraines, unexplained paresthesias (unsupported by

Myofascial pain syndrome, also known as "regional

EMG), and self-reported yet undetectable Raynaud

fibromyalgia," can manifest as localized myalgias or

phenomenon. "Symptomatic" mitral valve prolapse,

muscle spasms; patients can have localized tender points

and

in the muscles. The condition is considered different

"chronic fatigue syndrome" diagnoses tend to be comor

from fibromyalgia in that myofascial pain syndrome is

bid conditions. Remember, fibromyalgia can coexist

thought to originate from the injured muscle, whereas

irritable

bowel

syndrome,

interstitial

cystitis,

with autoimmune disorders such as SLE and RA. So,

comparable fibromyalgia pain is thought to originate

if an RA patient is not getting better despite aggressive

from an aberration in the CNS processing of pain.

immunosuppression and without clinical evidence for

Whiplash and repetitive microtrauma have been associ

inflammation on exam or labs, consider fibromyalgia as

ated with myofascial pain syndrome.

the cause of their pain.

Massage, physical therapy, muscle relaxants, NSAIDs,

Nonpharmacologic therapy is the foundation of FM

and local injection of anesthetic into the tender points

treatment. Physicians need to set realistic expecta

may be helpful.

tions with patients and reassure them that this is not a dangerous condition, while at the same time acknowl edging

that

their

pain/symptoms

are

real.

Stress

COMPLEX REGIONAL PAIN SYNDROME

reduction, cognitive behavioral therapy, and behavioral

Complex regional pain syndrome (CRPS), previously

feedback have been shown to help reduce symptoms.

known as reflex sympathetic dystrophy (RSD), is a form

Regular exercise and sleep restoration are essential

of chronic pain that usually affects a distal extremity

components of treatment.

(upper> lower).

2014 MedStudy

6-41

6-42

VASCULITIS

CRPS is divided into

types, both with similar signs

and symptoms: •

eosinophilic granulomatosis with polyangiitis [EGPA] or allergic granulomatosis).

CRPS 1: P reviously called reflex sympathetic dystrophy; this type accounts for

90% of the cases

and occurs after an illness or trauma in which the

•

polyangiitis (MPA), and Churg-Strauss syndrome (a.k.a.

Vasculitis is most often the result of an immune reaction caused by either immune complex deposition or com

nerves in the affected extremity were not directly

plement activation. It can affect small, medium, or large

damaged. Fracture is the most common trigger in

vessels. Often, vasculitis is hard to diagnose because

type I.

symptoms may be systemic and nonspecific.

CRPS 2: Ensues after a direct injury to the nerve.

Frequently, presenting signs/symptoms include myalgias/

In addition to pain, patients typically have sensory,

arthralgias, neuropathy, fever, malaise, and weight loss.

motor, or autonomic dysfunction manifested by pain,

Consider vasculitis in a patient with palpable purpura or

hyperalgesia, edema, temperature asymmetry, muscle

mononeuritis multiplex!

atrophy, decreased ROM, or weakness. The dysfunc tion often appears to be disproportionate to the inciting event. In severe cases, flexion contractures may develop. P rofound osteopenia may be seen on x-ray imaging. The diagnosis is clinical, but 3-phase bone scans may be helpful in diagnosing CRPS (sensitivity is

40-60%).

The most specific findings on bone scan include diffuse increased activity with juxtaarticular uptake on the delayed (phase 3) images. Although there have been limited studies evaluating the role of MRI in diagnos ing CRPS, MRI is often used to exclude other etiologies of localized pain. MRI has less sensitivity compared to triphasic bone scans. Treatment of CRPS consists of NSAIDs; pain modifiers, such as tricyclic antidepressants or gabapentin; physical therapy; short course of glucocorticoids; and sympathetic nerve block as needed. Early, aggressive therapy can prevent the chronic changes described above.

Because of the wide spectrum of symptoms, suspect vasculitis in patients with fever of unknown origin (FUO), especially in those with constitutional symptoms such as weight loss and fatigue. Also consider vasculitis in the differential diagnosis when there is no satisfac tory explanation for the following conditions: myosi tis, arthritis, palpable purpura (e.g., rash that does not blanch), mononeuritis multiplex manifested as foot drop, multisystem disease, glomerulonephritis, GI, cardiac, or CNS disease. Again, constitutional symptoms are big in vasculitis. (Rheumatoid arthritis eats at the joints and nips at the body; vasculitis nips at the joints and eats at the body.) Typical lab findings include an increased ESRICRP, thrombocytosis (the platelet count is a "poor man's sedi mentation rate"), anemia of chronic disease, and hypo albuminemia. Not all vasculitides present with elevated ESR or CRP ; e.g., primary CNS angiitis may have normal ESR and CRP!

OTHER CAUSES OF NONARTICULAR

Diagnosis of vasculitis is confirmed with biopsies or

RHEUMATI SM

angiograms. Skin biopsies may not be specific enough,

Other causes of myalgia: Alcohol is the most common

although polyarteritis nodosa can be diagnosed by skin

myotoxin and can cause acute rhabdomyolysis with very

biopsy in some cases. Muscle and nerve biopsies are

elevated CPK-MM. Hypothyroidism frequently pres

very specific, but not very sensitive-although sensi

ents with myalgias and stiffness and commonly has an

tivity increases with an increase in symptoms and with

elevated CPK-MM. Statins are also a relatively common

electromyogram (EMG) findings. Do a testicular biopsy

cause of muscle pain.

if the patient has testicular pain and/or swelling-sen sitivity and specificity are good. Kidney biopsies (in a patient with systemic vasculitis symptoms) showing a

VASCULITIS

necrotizing glomerulonephritis with crescent formation is virtually diagnostic for vasculitis (but may be seen

OVERVIEW

in several different vasculitic syndromes). Remember:

Vasculitis is the inflammation of blood vessel walls that

Biopsy the most involved tissue whenever possible.

can lead to narrowing, obstruction, ischemia, or aneu rysm formation. The clinical presentation is protean and varies according to the histologic type of inflammation, the size of the blood vessels involved, and the organs affected. Vasculitis is typically classified by the size of blood vessel affected and the presence (or absence) of antineutrophil cytoplasmic antibodies (ANCAs). The most common ANCA-associated vasculitides (AAV ) are granulomatosis with polyangiitis (GPA), microscopic

LARGE VESSEL VASCULITIS Overview Large vessel vasculitis includes:

Giant cell arteritis (remember, polymyalgia rheumatica

Takayasu arteritis

may coexist)

3) Aortitis

VASCULITIS

Don't wait for the biopsy! If you suspect GCA, treat right away to decrease the risk of vision loss. While the biopsy should be performed as early as possible, studies show that even a delay of 1-2 weeks doesn't significantly •

What are the typical lab findings in a patient

impact biopsy results. Biopsy a large piece of artery

with vasculitis?

(3-5 em) and do multiple cross-sectional cuts. Even so, because of the patchy involvement, a negative biopsy

What is a typical presentation of GCA?

•

does not exclude GCA. Bilateral temporal artery biopsies

What are the atypical presentations?

may improve sensitivity by about 5% compared to a uni

How do you diagnose GCA? What is a serious

•

lateral biopsy, but they

complication of GCA within the first 5 years

are

somewhat controversial.

If a patient with suspected GCA develops vision loss-a

of diagnosis?

medical emergency-treat the patient with high-dose IV methylprednisolone 1,000 mg/day for 3-5 days before

Giant Cell (Temporal) Arteritis

switching to oral glucocorticoids. Otherwise, initial

Giant cell arteritis (GCA), also called temporal arteritis,

treatment for GCA is prednisone at

is part of a spectrum of systemic inflammatory diseases

symptoms resolve, slowly taper to 20 mg/day over

associated with polymyalgia rheumatica (PMR).

60 mg/day. Once

1 month, then more slowly over the next 9-12 months.

GCA primarily affects the carotid arteries and their branches (ophthalmic and temporal) in patients

Most patients require prednisone for 2: 2 years, and relapses are especially common during the first year.

years of age (average age= 70 years). Female: male ratio

Follow the sedimentation rate because it frequently

is 3: I. The disease is most commonly seen in Caucasian

correlates

Northern Europeans and is rare in African-Americans.

decreases the risk of stroke in these patients, so this is

Multinucleated giant cells infiltrate blood vessels arising from the aortic arch in a patchy or segmental fashion. Symptoms include temporal headache, diplopia, amau rosis fugax, scalp tenderness, and jaw claudication. Jaw

with

disease

activity.

Low-dose

aspirin

started along with the steroids. Steroid-sparing agents may be used (especially in patients with diabetes or who are intolerant of steroids). Their efficacy, however, is controversial at this time.

claudication is a very specific symptom! Untreated,

The risk for aortic aneurysms is increased in patients

40-50% get ischemic optic neuropathy with unilateral

with GCA; risk is highest within the first 5 years of diag

irreversible blindness (increased risk in the setting of

nosis. Screening for aneurysms should be considered,

thrombocytosis; the risk may decrease by adding ASA).

particularly if they have additional risk factors (e.g.,

GCA occasionally has a masked presentation; consider it

tobacco use, hypertension, diabetes).

in workups for FUO, failure to thrive, and/or anemia of

GCA is a common exam topic. You may be given a case

chronic disease.

of an elderly Caucasian patient with shoulder aches, head

also

can

present

similarly

Takayasu's,

with

symptoms of large-vessel vasculitis and peripheral clau dication. Extracranial involvement in patients with GCA increases the risk of thoracic aortitis. Erythrocyte sedimentation rate (ESR) is virtually always >

60 mmlhr in GCA; and in patients whose ESR is not

elevated, C-reactive protein (CRP) may be elevated. While extremely rare, GCA can occur even in the setting of a normal ESR and CRP. Confirm (Image

diagnosis

temporal

artery

biopsy

6-19). Ultrasonography of the temporal arter

ies has been studied as a means of diagnosing GCA. However, racy

the the

dependent

accu test

ache, and vision complaints. You must determine whether the patient has polymyalgia rheumatica (PMR) with GCA, retinal artery occlusion, carotid artery disease, or some ophthalmic disorder. Body pain+ vision complaints in the elderly + high sed rate

PMR with GCA! Also

know that GCA can present as a FUO or weight loss in the elderly.

Polymyalgia Rheumatica Polymyalgia rheumatica (PMR) is a clinical syndrome that is classically associated with giant cell arteritis and may be a milder manifestation of the same disease. 20% of PMR patients develop GCA. Conversely, in those with GCA, 50% also have symptoms of PMR or have

already been diagnosed with PMR.

the

skills of the technician

A PMR-like illness can be present in other conditions.

and

interpreter.

Elderly-onset RA can present as a syndrome indistin

Glucocorticoid therapy

guishable from PMR initially, although a significant

the

is started as soon as the

inflammatory polyarthritis eventually develops. (RF is

diagnosis is suspected.

often negative.) Presence of an otherwise unexplained fever in a patient with PMR may indicate the develop ment of GCA.

Image 6-19: Inl f amed temporal artery

6-43

6-44

VASCULITIS

Think of PMR in the older patient with a history of

stage.

profound morning stiffness, bilateral shoulder girdle and

or bypass surgery may be needed for severely stenotic

hip aching, and hand swelling (mimicking R A).

Revascularization

with

angioplasty,

stenting,

arteries. Ideally, these procedures should be performed

Remember: PMR pain is out of proportion to exam findings. PMR presents with aching and stiffness, not weakness-in contrast to myositis, which generally presents with weakness, not pain! In addition, PMR is

when

the

acute inflammatory phase is

controlled.

Patients may require antiplatelet or anticoagulation for very stenotic vessels. Takayasu arteritis tends to recur and has a guarded prognosis.

distinguished from polymyositis by the absence of both

Cardiovascular disease is the major cause of death in

objective weakness and elevated muscle enzymes. CK

Takayasu arteritis. Strict management of traditional

is normal in PMR even though the muscle aches and the

cardiovascular risk factors is mandatory. Remember: A

patient feels stiff.

patient with history of Takayasu may present with low BP

Sedimentation rate is typically elevated but may be normal in

�

50 mrn/hr)

in one arm, but don't forget to check the BP in the other arm

5%.

Treatment: PMR responds dramatically to low-dose prednisone (about 10---20 mg/day), although it must be slowly tapered, usually over 2-3 years for cure. If the

and both legs. Hypertension may be undetected and

not appropriately treated in these patients!

Aortitis

exam gives you an older patient with shoulder pain who

Aortitis is associated with several systemic inflammatory

improves dramatically overnight after 1-2 doses of pred

diseases. Exam questions typically ask about the most

nisone, the diagnosis is PMR. PMR may occasionally

common

respond to NSAIDs, but risk for PMR turning into GCA

mycotic aneurysm, GCA/Takayasu, and spondyloar

is increased if inflammation is not controlled.

thropathies. IgG4-related disease is a relatively new

In atypical cases of PMR, especially those individuals who do not respond to low-dose glucocorticoids (I 0---20 mg/day with dramatic response expected within 1-3 days), think GCA or an alternative diagnosis, such as cancer. As with GCA, the ESR correlates with disease activity;

associations:

syphilis,

endocarditis

with

disorder known to cause aortitis. Know that syphi litic aortitis is a tertiary manifestation associated with aneurysm formation and valve regurgitation, but aortic dissection and rupture are extremely rare!

so, follow it during treatment. If there are any signs of

MEDIUM I SMALL ARTERY VASCULITIS

GCA (e.g., visual changes, headache), you must do a

Overview

complete reevaluation immediately, including temporal artery biopsy and an increase in the prednisone dose.

Takayasu Arteritis Takayasu

arteritis

("pulseless

disease")

commonly

involves the aorta and its proximal branches. It primar ily affects young women

40), particularly of Asian

descent. This may present initially with nonspecific inflammatory features such as a FUO (inflammatory phase); then, months to years later, with claudication of the upper extremities, strokes, TI As, or renovascular

Most common and frequently tested medium/small artery vasculitides:

Polyarteritis nodosa (PAN)

Churg-Strauss (allergic eosinophilic granulomatosis with polyangiitis [EGPA])

3) Granulomatosis with polyangiitis (GPA, previously "Wegener granulomatosis") 4) Microscopic polyangiitis (MPA) Of these four, know that PAN is the only one not

hypertension with bruits ("pulseless phase"). Patients

associated with ANCA autoantibodies.

also may have Raynaud's, erythema nodosum, and aortic

Review the material on AN CAs on page 6-2.

regurgitation from dilatation of the ascending aorta. Diagnose

using

conventional

angiogram

angiogram (MRA) demonstrating large artery narrowing, referred to as "beading" or "string of pearls," and/or characteristic aneurysms. Exacerbations or recurrences of inflammation are indicated by an increase in the ESR/ CRP, anemia, and artery wall inflammation visible on MRA. Unlike GCA and many of the other vasculitides, tissue biopsy has little role in the diagnosis of this disor der. (Trying to nick the aorta for a tissue sample

really

bad idea!) Treat

with

glucocorticoids

(main)

DMARDs.

Biologics have been used to treat the acute inflammatory

Polyarteritis Nodosa Polyarteritis

nodosa

(PAN)

affects

medium-sized

arteries and is strongly associated with hepatitis B. The vasculitis results in inflammation in the walls of arteries (but not capillaries or veins) with subsequent formation of aneurysms. Unlike many of the other vasculitides, the inflammation in PAN is not granulomatous; instead, it is marked by the accumulation of neutrophils and mononuclear cells with fibrinoid necrosis. Classic PAN commonly affects the arteries that supply the skin, peripheral nerves, GI tract, and kidney, but spares the lungs. Symptoms of PAN include anorexia

VASCULITIS

These symptoms and a positive ANCA, especially with a positive anti-PR3, are more consistent with a diagnosis of granulomatosis with polyangiitis (GPA)-definitely not PAN. •

What are differences in the clinical presentations

Treatment of PAN includes treating chronic HBV, if

of myositis and PMR? •

present, and giving prednisone +/- cyclophosphamide, depending on severity at presentation. IV cyclophos

How does the treatment of PMR differ from the

phamide-pulse therapy may be less effective at induc

treatment of GCA? •

ing a sustained remission, but it is tried because toxicity

With which virus is PAN associated?

is less. PAN is a severe disease, and patients die if not

•

How do you diagnose PAN?

treated

•

Which organs/tissues are commonly involved

only slows the progression of the disease.

in GPA?

There is a skin variant termed "cutaneous PAN" that

(10-20% survive 5 years). Sometimes, treatment

has skin lesions and neuropathy as clinical features. with weight loss, fevers, malaise, arthralgias, mononeu

The skin lesions can be severe and ulcerative, so

ritis multiplex, CNS symptoms, abdominal symptoms,

immunosuppression may still be required.

and lower extremity rashes (palpable purpura, livedo reticularis, nodules, and bullae/vesicles). The abdominal symptoms are related to mesenteric arteritis, causing infarct or perforation. Renal involvement usually pre sents as hypertension, mild proteinuria, and hematuria

Eosinophilic Granulomatosis with Polyangiitis (a.k.a. Churg-Strauss Vasculitis) Eosinophilic granulomatosis with polyangiitis (EGPA)

without red cell casts. Note: PAN does not cause glo

is a necrotizing, pulmonary-renal vasculitis marked by

merulonephritis; thus, the absence of RBC casts. Instead,

eosinophilic granulomas. Patients typically have a history

disease affects the walls of the arteries that supply blood

of severe asthma +/- sinus disease or allergies (including

to the nephron. Essentially, renal ischemia is the primary

allergic rhinitis and nasal polyps). Mononeuritis multi

pathology, with activation of the renin-angiotensin

plex is particularly common. Glomerulonephritis is less

aldosterone system and development of hypertension.

common compared to GPA or MPA.

PAN can affect virtually all organ systems, including

Lab:

the coronaries. But PAN does not classically cause

anti-MPO+.

disease of the pulmonary arteries nor does it cause glomerulonephritis! Patients may present with pulmo nary edema as a consequence of left heart failure, but PAN does not cause pulmonary hemorrhage or infarc

peripheral

eosinophilia

10%,

p- ANCA+,

Treatment is the same as for PAN, although many patients respond well to glucocorticoids alone.

tion. These tidbits help you exclude PAN as a cause of

Granulomatosis with Polyangiitis

a pulmonary-renal vasculitis. If you see a patient with a

The hallmark of granulomatosis with polyangiitis (GPA)

pulmonary-renal vasculitic syndrome, you should think GPA, MPA, or EGPA-not PAN!

tis that commonly involves the sinuses causing a "saddle

Suspect a diagnosis of PAN in a patient with multiple diverse symptoms; e.g., chest pain (pericarditis), abdom inal pain (mesenteric arteritis), foot drop (mononeuritis multiplex), and testicular pain. Diagnosis of PAN: If there is no obvious peripheral involvement

(e.g.,

nerve,

muscle,

testicle),

angiogram. An angiogram of the mesenteric or renal medium-sized arteries can show diffuse, small, saccu lar aneurysms or stenoses that are diagnostic. If there is peripheral involvement,

biopsy the affected site.

Again, biopsy the testicle(s) if pain is present. If there is mononeuritis multiplex, biopsy the sural nerve. If the kidney is affected in PAN, the involvement is in the artery, and biopsy is frequently diagnostic. (Remember: This is not glomerulonephritis.) Important to note: ANCA tests are usually negative. Test for hepatitis B infection whenever PAN is suspected.

is necrotizing granulomas; this is a small vessel vasculi nose deformity," lungs with cavitary nodules, and kid neys (a classic pulmonary-renal syndrome). Patients occasionally develop skin rashes and/or ulcerations and may have migratory large joint arthritis (Image

6-20).

Recurrent sinusitis and other upper respiratory issues are extremely common. Sinus tissue biopsy in GPA can show any of these follow ing 3 findings:

I) Small vessel vasculitis 2) Necrosis 3) Granulomatous inflammation The biopsy yield is low because only 3�0% of patients have any

1 of these findings and only 15% have all 3.

Even so, the site of any oral, nasal, or sinus abnormality is the preferred I" biopsy site because it's the least inva sive. Among the organs commonly involved in GPA, lung biopsy followed by kidney biopsy has the highest diagnostic yield.

6-45

6-46

VASCULITIS

Remember the antibody tests, page 6-1 : Patients with GPA are often c-ANCA+ and anti-PR3+. This helps exclude Goodpasture syndrome, which is caused by anti-glomerular basement membrane (GBM) anti bodies. Of interest, patients who are anti-GBM+ and c- ANCA+ have a better prognosis than those who are only anti-GBM+.

Prescribe trimethoprirn/sulfamethoxazole because of increased risk for Pneumocystis jiroveci pneumonia ([PJP] formerly known as PCP). It is unknown whether it is the illness itself or the cyclophosphamide treatment that predisposes these patients to PJP, but preventing this lung infection may help prevent GPA-associated lung exacerbations.

c-ANCA+ is seen in > 90% of patients with diffuse GPA, but in only 50% with limited GPA. (Limited typically= no renal involvement.) ANCAs occasionally appear in rapidly progressive glomerulonephritis (which can be considered renal involvement of the vasculitis) and in microscopic polyangiitis ([MPA] discussed next), but these vasculitides are usually p- ANCA+ and MPO+.

Remember: Side effects of cyclophosphamide include short-term problems, such as bone marrow suppres sion and infection, and longer-term problems, such as sterility, amenorrhea (higher risk > age 35), bladder effects (hemorrhagic cystitis and cancer), and leukemia/ lymphoma.

The diagnosis of GPA is made with biopsy. If the patient has no upper respiratory abnormalities appropriate for biopsy, then biopsy either the kidney or the lung, depend ing on which is most affected and which biopsy the patient can best tolerate. Renal biopsies are not specific enough to allow differentiation between GPA and microscopic poly angiitis, but the differentiation is not important because the treatment is identical. The point is to get tissue that has an artery in it for diagnosis of vasculitis.

Microscopic Polyangiitis

�

GPA, like PAN, rapidly progresses to death without treatment. Therapy consists of high-dose steroids and cyclophosphamide or rituximab, with the latter being approved by the FDA in 2011. In clinical trials, ritux imab demonstrates efficacy for GPA even in severe cases that are refractory to cyclophosphamide; toxicity of the drug is less than that of cyclophosphamide. In patients with mild pulmonary and renal involvement (defined as normal oxygenation and < 50% increase in creati nine), methotrexate, azathioprine, and leflunomide have been used.

Microscopic polyangiitis (MPA) is also a pulmonary-renal syndrome with glomerulonephritis being much more common than pulmonary capillaritis. MPA causes a necrotizing, crescentic glomerulonephritis and may present as a FUO. In contrast to GPA and EGPA, granulomatous inflammation is absent. GPA and MPA are referred to as "pauci-immune" vasculitides since immune complex deposition is not detected to any significant degree, unlike in SLE. MPA never has angie graphic changes since it involves small vessels. Upper airway and pulmonary nodules are not typical of MPA and when present suggest GPA. Diagnosis is based on biopsy of affected tissue. MPA is often p-ANCA+ and MPO+. Treatment is essentially identical to GPA. Rituximab is also approved for the treatment of MPA. OTHER SMALL-VESSEL VASCULITIDES Overview

Other important small vessel vasculitides to remember include: •

•

Hypersensitivity vasculitis (leukocytoclastic vasculitis) Henoch-Schonlein purpura (lgA vasculitis) Cryoglobulinemia Anti-glomerular basement membrane disease

Hypersensitivity Vasculitis

Image 6-20: Nodules in granulomatosis with polyangiilis (GPA)

Hypersensitivity vasculitis is a confusing term. It is appropriately used to define a small vessel vascu litis of the skin with minimal or no involvement of other organs. On biopsy, these skin lesions typically display "leukocytoclastic vasculitis," which is the his topathological correlate for hypersensitivity vasculitis. Leukocytoclastic vasculitis refers to PMNs permeating through vessel walls with concomitant cellular death and debris. Although the lesions may not always be palpa ble, the classic skin manifestation is "palpable purpura"

VASCULITIS

Diagnosis can be confirmed by identifying the presence of IgA deposits in the vessel wall on skin biopsy. It is

Q�uiz •

•

usually benign and resolves spontaneously but occa sionally causes renal failure (up to I 0% of adults and

Which antibodies are specific for GPA?

Why is trimethoprim/sulfamethoxazole given

is often supportive.

but there is no compelling evidence that they help

to patients with GPA? •

5% of children). Treatment

Glucocorticoids may improve joint and GI symptoms, kidney disease. Give corticosteroids or cytotoxic agents

Leukocytoclastic vasculitis is associated with

only for life-threatening symptoms.

which diseases? •

Mixed cryoglobulinemia is associated with

Cryoglobulinemia

which hepatitis virus?

Cryoglobulins are immunoglobulins that precipitate in

("crops" of purple papules or large petechiae), most often seen on the lower extremities. About

40-50%

vasculitis

include: Drug reactions (especially beta-lactams, sulfonamides, NSAIDs, diuretics, phenytoin, and allopurinol) •

98.6° F and redis

solve when warmed. Cryoglobulins are normally cleared by the liver. Buildup occurs with overproduction or

hypersensitivity

idiopathic, but the most common identifiable causes

•

a serum specimen when chilled

Infections (e.g., viral hepatitis, beta-hemolytic strep, HIV, endocarditis)

decreased elimination from chronic liver disease. There are 3 types of cryoglobulinemia: Type I is least common

(I 0-15%). It is due to a single

monoclonal antibody (lgM, IgG, or IgA) and is usually found in patients with multiple myeloma or Waldenstrom macroglobulinemia. Type I does not have rheumatoid factor activity like

Other causes of small-vessel vasculitis, discussed below,

Types II and III; hence, complement is not activated.

must be excluded.

Therefore, patients are typically asymptomatic until the

Hypersensitivity vasculitis due to a drug reaction can occur

cryoglobulin level rises high enough to cause symptoms

1-10 days after drugs are started. Keep in mind the rash may occur after the drug has already been discontinued (as

antibiotics).

Treatment

hypersensitivity

vasculitis involves treating the underlying condition, or

of hyperviscosity such as neurologic symptoms (head ache, blurred vision, vertigo, deafness, nystagmus), livedo reticularis, purpura, and Raynaud phenomenon. Type II is most common (50-60%). It is considered a

when known, discontinuing the causative medication.

mixed cryoglobulin where the immune complex consists

In idiopathic cases, hydroxychloroquine, dapsone, or

of monoclonal lgM rheumatoid factor attached to poly

colchicine can be tried. Glucocorticoids can be used for

clonal IgG. Most patients have an associated hepatitis

more resistant disease.

C (HCV ) infection. Patients who do not have HCV but

The

histopathological

finding

"leukocytoclastic

vasculitis" can also be found on skin biopsy with

have these cryoglobulins are considered to have "essen tial" mixed cryoglobulinemia.

vasculitides that affect other organs in addition to the skin,

Type Ill (25-30%) is similar to Type II in that it is also

such as IgA vasculitis or cryoglobulinemia.

a mixed cryoglobulin, but has immune complexes typi

Henoch-Schonlein Purpura (lgA Vasculitis)

and polyclonal IgG. 1/2 of patients have HCV infection,

cally composed of polyclonal IgM rheumatoid factor

Henoch-Schonlein purpura (HSP) is an IgA-mediated, small-vessel vasculitis that can affect arterioles, capil laries, and venules. Organs affected often include: the skin from the waist down (crops of papules, "palpable

and the others usually have a chronic autoimmune disor der(e.g., SLE) or a lymphoproliferative malignancy. A low C4 out of proportion to C3 is a clue to the presence of cryoglobulins.

purpura"), kidneys (biopsy findings identical to IgA

Types II and Ill cryoglobulinemia produce similar symp

nephropathy), GI tract (abdominal pain and bleeding,

toms. They both activate complement and frequently

intussusception), and joints (typically the knees and

present with a small vessel vasculitis, most commonly

ankles). Most cases are self-limited; about 20% have a

with

repeat attack, and 5% develop chronic HSP. About 75%

peripheral

lower

extremity neuropathy,

purpura, and

glomerulonephritis,

hypocomplementemia.

of cases are in children, predominantly those 2-11 years

Patients may eventually get hyperviscosity symptoms

old; 25% in adults. Upper respiratory and streptococcal

discussed in Type I.

infections often precede HSP (hence a peak in incidence during autumn and winter months), but foods, medica tions, and insect bites have been linked to this vasculitis. IgA levels may be elevated.

Patients with HCV and mixed cryoglobulinemia (Types II and III) can get membranoproliferative glomerulo nephritis (MPGN). These patients have low C3, C4, and CH50 (classical complement activation), and their

6-47

6-48

VASCULITIS

rheumatoid factor (RF) is very high (because Types II

Remember the pulmonary-renal syndromes (rheumatic

and III are RFs). MPGN frequently causes renal failure.

diseases

When the patient gets renal disease, prognosis is poor.

glomerulonephritis):

Cryoglobulin assays are difficult to perform, and false negative rates are high. When possible, do a skin biopsy

•

and send for histology and direct immunofluorescence

•

(DIF), which can reveal the type of immunoglobulin and

(+/- new protease inhibitors) is often effective for the vasculitis caused by HCV. In patients with more severe

can

cause

alveolar

hemorrhage

and

Goodpasture syndrome CTD: SLE, RA, PM or DM, PSS

•

Systemic vasculitis: GPA, MPA, EGPA, HSP,

•

Drug-induced: propylthiouracil (PTU)

•

Beh9et disease

•

Cryoglobulinemia

Churg-Strauss

complement deposition. Treatment with pegylated interferon alfa and ribavirin

that

disease (visceral or renal), glucocorticoids or more potent agents may be required. Rituximab has been used off-label effectively.

BEHCET DISEASE Beh9et disease is a unique vasculitic syndrome that can

DDx: Do blood cultures to exclude endocarditis. Other

affect any organ and vessels of any size, although it has

diseases that mimic this form of vasculitis include

a predilection for veins. It primarily affects young adults

cardiac atrial myxoma emboli and cholesterol athero

in their 20s to 30s who live in the Middle East or Asia,

embolism. Obtain an echocardiogram when emboli are

and is rare in North America. The diagnosis is made

suspected.

clinically because there is no pathognomonic laboratory

Especially consider cholesterol atheroem

bolism in a patient with severe atherosclerosis who has

test, though HLA-B51 and HLA-B5 have been associ

just had an arteriogram. This is important if the patient

ated with this disease. Ulcers are very painful (whereas

has hypereosinophilia (90% of patients) and/or hypo

in SLE, ulcers are typically painless). Current interna

complementemia (50% of patients). Skin biopsy of

tional criteria for the diagnosis of Beh9et's include:

punctate lesions can confirm the diagnosis of cholesterol atheroembolism.

Recurrent oral ulceration plus 2 of the following:

Recurrent genital ulceration

2) Ocular lesions (uveitis, retinal vasculitis)

ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE I GOODPASTURE SYNDROME

Anti-glomerular basement membrane (GBM) disease

The pathergy test is fairly specific for Beh9et's but not

3) Skin lesions (erythema nodosum, acneiform nodules)

results from anti-GBM antibodies that deposit in the pulmonary and/or glomerular capillaries. The clinical presentations include a rapidly progressive glomerulo nephritis without lung involvement (termed "anti-GBM disease") or a rapidly progressive glomerulonephritis with pulmonary hemorrhage (Goodpasture syndrome). Goodpasture's

has

bimodal

20-30 years (M > F) and 60-70 years

age

distribution: M). Smoking

has a strong correlation with alveolar hemorrhage, especially in young males. antibodies in the serum and with renal and/or lung which

will

demonstrate

evidence

stick. A positive pathergy test also can occur in pyodenna gangrenosum. Peripheral arthritis is common and patients can develop a gastrointestinal disorder that mimics Crohn disease (due to intestinal ulcerations or mesenteric vasculitis). The most serious complications include blindness, CNS disease (meningoencephalitis, cranial nerve palsies, vessels. First-line therapy for oral and genital ulcers includes

the

topical/oral glucocorticoids. Sucralfate suspension can

15% of patients who are anti-GBM+ also are ANCA +

cine with thalidomide, which is reserved for more seri

anti-GBM antibodies on immunofluorescence. �

very sensitive: The patient develops a sterile papule or ulcer 1-2 days after minor trauma, such as a needle

seizures), and thrombosis or rupture of large aneurysmal

Diagnose anti-GBM disease by measuring anti-GBM biopsy,

Positive pathergy test ("skin prick test")

also be used. First-line oral therapy should be colchi

and can have symptoms of systemic vasculitis. These patients with double antibodies are treated the same as patients with anti-GBM only and tend to have a better prognosts. Remember that patients with pulmonary hemorrhage

ous mucous membrane involvement given its significant side effect profile. Treat more severe disease (vascular or neurologic) with systemic corticosteroids, azathio prine, cyclophosphamide, and anti-TNF biologic agents. Relapse is common.

may have an increased DLCO. Treatment involves plasmapheresis to remove circulating anti-GBM

antibodies

and

immunosuppression

with

glucocorticoids and cyclophosphamide to inhibit further autoantibody formation.

RHEUMATOLOGIC ISSUES ASSOCIATED WITH MALIGNANCY AND DIABETES MELLITUS

systemic sclerosis causes thickening of skin proximal to the metacarpals in addition to the fingers.) On physical exam, the "prayer sign" may be seen. This is the inability to press the palms together completely •

•

What are the clinical features of Beh9et's?

without a gap remaining between opposed palms and fingers.

What complications can be seen with Behyet's? •

RELAPSING POLYCHONDRITIS

•

Relapsing

polychondritis

(RP)

inflammatory

disorder of cartilage (ear, nose, larynx, and trachea) and tissues rich in proteoglycans (eyes and heart valves). While

Carpal tunnel syndrome Frozen shoulder Foot disorders that include neuropathic arthropathy (page 6-32)

•

Osteomyelitis

is most often a primary disorder, it

PAGET DISEASE

is frequently associated with other diseases, most com monly some form of systemic vasculitis, connective tissue disease, or myelodysplastic syndrome. Patients

present

with

unilateral

bilateral

ear

inflammation which can mimic cellulitis, except that the ear lobe is spared (no cartilage). It also can cause arthri tis, ocular disease (scleritis, iritis), hearing loss/vertigo, and vasculitis (10-20%).

can cause aortic dilatation

and a valvulitis leading to aortic and/or mitral regurgi tation. Skin findings are frequent and can mimic those found in Behyet's. relapsing polychondritis) characterized by mouth and genital ulcers with inflamed cartilage. Suspect in a patient presenting with hoarseness, saddle-shaped defor mity of the nose, and swelling of the ear's cartilage with sparing of the ear lobe. are

the

cornerstone

treatment.

Occasionally, steroid-sparing agents are required.

9 ri 9

RHEUMATOLOGIC ISSUES

ASSOCIATED WITH MALIGNANCY AND DIABETES MELLITUS

h ta

Malignancy (also see Oncology, Book 4) is associated with: •

Hypertrophic pulmonary osteoarthropathy (HPOA) (page 6-32)

•

Amyloidosis (check with rectal biopsy or an abdominal fat pad biopsy)

•

Secondary gout

Carcinomatous polyarthritis (resembles RA; especially consider with breast cancer or leukemia)

Diabetes mellitus (see more in Endocrinology, Book 4) is associated with: •

Osteoarthritis.

V d ti e n U •

•

Fractures, including stress fractures.

Serum alkaline phosphatase and urinary

hydroxyproline are elevated because both of these

are indications of increased bone turnover.

•

Osteosarcoma occurs in about I%!

First-line treatment for Paget disease is bisphospho

MAGIC syndrome is an overlap disorder (Behyet's and

Glucocorticoids

G R

Paget disease of the bone (see Geriatrics in General Internal Medicine, Book 5) is associated with:

nates. Teriparatide should not be prescribed for these

patients because it is associated with osteosarcoma, and patients with Paget's are already at increased risk for this

condition.

AMYLOIDOSIS

Amyloidosis

results

from

abnormal

deposition

autologous extracellular proteins into organs and tissues, causing a disruption of function. Symptoms can include

joint pain, macroglossia with dysphagia, polyneuropathy, congestive heart failure, and renal and liver dysfunc tion. Different types of amyloidosis have been described based on site and pathology of the lesions.

Reactive systemic AA amyloidosis (secondary amy loidosis; fibrils composed of serum amyloid A [SAA] proteins). This can be a long-term consequence of chronic inflammatory diseases like RA, Crohn's, juve nile idiopathic arthritis, autoin:flammatory syndromes, malignancies, and infections. The kidneys are most commonly involved, followed by the liver and spleen. Very rarely are the heart and nervous system affected.

AL (primary) amyloidosis results from monoclo nal immunoglobulin light-chain (L for Light) depo sition (typically, lambda light chains). This type of amyloidosis is commonly seen in patients with smolder

Dupuytren/:flexion contractures: occur in poorly

ing myeloma (e.g., MGUS). Any organ except the CNS

controlled longstanding diabetes mellitus. This and

can be involved. At time of diagnosis, the kidney (66%)

the preceding limited joint mobility are known as

and heart (50%) are commonly affected.

cheiroarthropathy. This may also present with thickening of the skin of the fingers. (Remember that

Dialysis

associated

complication

from

(AB2M)

amyloidosis

long-term

hemodialysis

where

6-49

6-50

OFFICE ORTHOPEDICS

�2 microglobulin is not cleared by dialysis. After about 5-7 years of dialysis, patients develop symptomatic lesions,

often

involving

bones/joints;

visceral

and

vascular deposits also can occur. of

transthyretin

(transthyretin-related

amyloidosis; hence ATTR); deposition occurs in those>

70 years of age and is universal in those > 90. Typically, deposits are

microvascular,

aspect, just inferior to the knee. Pes anserine bursitis is described as pain +/-swelling� 2 em inferior and medial

Senile systemic amyloidosis (ATTR amyloid). Fibrils are composed

(suprapatellar, infrapatellar, prepatellar, and pes anserine), and that the pes anserine bursa is located on the medial

but

when the heart

involved, congestive heart failure can occur. Biopsy of affected tissue is the gold

to the patella. In all locations, there is frequently a sero sanguineous effusion within the bursal sac. More infor mation on these bursitis presentations is included later in this section. Diagnosis is usually clinical but requires exclusion of infectious bursitis if the area is inflamed and/or the patient

standard to

confirming the presence of amyloid. The pathognomonic finding is "apple green-red birefringence" when stained with Congo red dye and viewed under polarized light. Abdominal fat pad aspiration has been studied as a tool to detect senile systemic amyloidosis. It has a sensitivity of 80--90%, and a specificity of I 00%. Serum amyloid P

is systemically ill, especially in patients on immunosup pressants; e.g., patients with RA on chronic corticoste roids. Aspiration of the bursa with fluid studies, including

G R

Gram stain and culture, helps you determine whether infection is present. If no sample is obtained for micro biology, empirical treatment with an antistaphylococcal drug may be necessary.

(SAP)-Iabeled scintigraphy is useful to evaluate the

Treatment

whole body burden and distribution of amyloid.

Glucocorticoids can be injected, provided that the

consists

V d ti e

rest

the

affected

area.

bursa is not infected. Mild infection in immunocompe

Therapy is 2-fold:

I) Maintenance of organ function or replacement of organ 2) Reduction/elimination of fibril precursor protein (e.g., control the underlying inflammatory process-treat the RA, malignancy, etc.)

tent patients can often be treated with oral antibiotics, but serious infections in immunocompromised patients should be treated parenterally. Resistant, chronic cases sometimes require surgical excision of the bursa.

n U -

JOINT PAIN

OFFICE ORTHOPEDICS

Overview

Joint pain can be caused by a problem within the joint, a

OVERVIEW

problem with associated ligaments or tendons, or inflam

Know this section very well. The common aspects of

office orthopedics and rheumatology will very likely be

9 9

on the exam.

r i h

OSTEOPOROSIS

BURSITIS

When an extremity joint is acutely swollen without a

history of trauma, it should be tapped and analyzed for

crystals, cell count with differential, and Gram stain with culture.

Osteoporosis is covered in General Internal Medicine, Book 5, under Geriatrics.

mation of a bursa (just discussed).

Remember the mnemonic for the 3 Cs: cell count, crystals, and culture.

Bursae are small fluid-filled sacs that provide a gliding surface to reduce friction when muscles and tendons slide across bone. Healthy bursae are necessary for a smooth, frictionless surface making normal move ment painless. Bursitis is the inflammation of a bursa secondary to mechanical irritation, bacterial infection, RA, gout, or pseudogout. Bursitis or tendonitis usually

causes severe pain with any active movement of the

Lateral

joint-especially against resistance. Passive range of motion is much less painful, or even painless.

Rotator cuff tear

Prepatellar bursitis (housemaid's knee or clergyman's

Impingement syndrome

knee), olecranon bursitis (student's elbow), trochanteric

Frozen shoulder

bursitis, subacromial bursitis, and pes anserine bursitis

Cervical radiculopathy

are the most frequently tested-probably because they are the most common. Know that the knee has several bursae

Figure 6-3: Shoulder Lateral V1ew

OFFICE ORTHOPEDICS

neurogenic TOS: Patients abduct their arms to 90 degrees while elbows are flexed at 90 degrees; then they open and close their hands for 3 minutes. If they cannot maintain this position due to symptoms, the test is •

positive.

Name some bursae that commonly become inflamed.

•

The Adson test is another common maneuver used to evaluate for vascular TOS. Locate the patient's radial

What is the workup for nontraumatic arthritis?

pulse while the patient turns their head toward the tested shoulder. The patient then extends their neck while

A word about terminology:

the examiner laterally rotates and extends the patient's

•

Abduction

away from the midline.

•

Adduction

toward the midline.

•

Dorsiflexion =pulling the foot upwards, as in taking

if there is loss of the radial pulse and reproduction of

the foot off the gas pedal.

TOS symptoms. If you suspect the syndrome, do a chest

Plantarflexion

radiograph (looking for cervical ribs that sometimes are

•

shoulder with the arm straight. The patient then takes in a deep breath and holds it. The test is considered positive

pressing the foot down, as in press

G R

a cause) and/or EMGs with nerve conduction studies to

ing on the gas pedal.

see if the brachial plexus is affected.

Shoulder

V d ti e n U

Treat with shoulder exercises and education about

True shoulder pain usually extends from the acromion to the insertion of the deltoid. Refer to Figure 6-3 through Figure 6-5 as you read this topic. Many of the shoulder syndromes affect the glenohu meral joint and limit range of motion due to pain. This is demonstrated by the "painful arc" test. In this test, the patient actively raises the arm laterally from the side to an overhead position. Pain-induced limitation of motion in the middle of the arc indicates a positive test.

avoiding the postures that elicit symptoms. Cervical ribs can be surgically removed if they are the cause.

ShoulderOA

Primary OA in the shoulder is rare unless repetitive use of the joint and trauma is the contributing factor, which is much more common in the acromioclavicular (AC) joint than in the glenohumeral joint. Pain in AC joint arthritis is usually localized over the AC joint, while the pain in glenohumeral arthritis can be anterior in the

ThoracicOutlet Syndrome Thoracic

outlet

syndrome

(TOS)

results

from

compression of the neurovascular structures supplying

9 ri 9

the upper extremity. Problems in the neck/shoulder can cause irritation of the brachial plexus as it moves from

the neck and chest cavity into the arm. Impingement of

shoulder or nebulous and ill-defined. Although x-ray films can appear normal early on, they may show joint space narrowing and osteophytes over time. Treat as you would all cases of OA with education and nonnarcotic

analgesics. Surgery is used only in very refractory cases.

the nerves causes shoulder pain that may be localized

Amyloidosis

or extend from the base of the neck, over the top of the

Long-term dialysis patients are likely to get amyloid

shoulder, and down the arm. This pain may extend into

deposition (beta-2 microglobulin) in the joints. This

h ta

the hand and is often accompanied by paresthesias and

causes painful joints and tends to affect the shoulder and

weakness. If the vascular supply (subclavian/axillary

wrist, causing carpal tunnel syndrome.

vessels) is also affected, patients will have hand claudi cation+/- Raynaud's and ulcers in severe cases.

TOS has been classified into 3 categories based on etiology, symptoms, clinical presentation, or anatomy:

1) Arterial TOS (1 %; digital ischemia, claudication, typically related to a cervical rib) 2) Venous TOS (2-3%; due to subclavian vein obstruction from thrombosis/scarring, upper limb swelling is common) 3) Neurogenic TOS (95%; brachial plexus is compressed; paresthesia and pain in the neck, shoulder, and arm are common; symptoms are worse with overhead motion) Diagnosis is difficult because PE is usually normal unless provoked by certain maneuvers. The elevated arm stress test (Roos test) is a good test to detect

Adhesive Capsulitis or "Frozen Shoulder" This condition is most commonly seen in patients who are 40--60 years of age and who typically have an under lying predisposition; e.g., chronic bursitis/tendonitis, fracture, or rotator cuff injury. Diabetes and thyroid dis ease are also risk factors. However, adhesive capsulitis can occur in the absence of any apparent cause. Diagnosis is suggested by shoulder pain, stiffness, and decreased range of glenohumeral motion in all direc tions. PE shows significantly reduced range of motion

(< 50% of normal), both actively and passively, in all directions. Radiographs are often normal. Symptoms usually resolve in 1-2 years. Physical therapy and range of motion exercises are important to help

6-51

6-52

OFFICE ORTHOPEDICS

patients regain their function. lntraarticular corticoste

If strength is normal, conservative management is best

roids are occasionally used. Refractory cases may require

initially: rest from aggravating activities, ice, and physical

surgery (< I 0% of cases).

therapy for 3 months. Treat the pain with a short course

Impingement Syndrome

sometimes are used if the patient doesn't get better

This syndrome refers to compression of the subacromial bursa or regional tendons in the space between the acro mion and the humeral head. The biceps tendon and all of the rotator cuff tendons go through this area. For this reason, bicipital tendonitis and some rotator cuff injuries

NSAIDs.

Intraarticular

glucocorticoid

injections

quickly. Refer for orthopedic evaluation if the patient still has pain after 3 months of therapy or if weakness/muscle atrophy is present at initial evaluation, which might suggest a rotator cuff tear.

are often considered impingement syndromes. Impingement typically causes pain when the patient

Subacromial Bursitis

G R

reaches overhead or sleeps on the affected shoulder.

This is also called deltoid bursitis. Patients present with

Except in longstanding cases, strength in the shoulder is

pain both at rest and with movement. The pain with

normal. As

this bursitis is referred to the lateral aspect of the arm.

with

several

other

shoulder

syndromes,

these

patients have a positive painful arc test. For diagnosis of impingement syndrome, use the following provocative maneuvers that are more specific. If any of the following

Consider this diagnosis when the patient reports waking from sleep with pain in the shoulder and arm. It can be

V d ti e

associated with a rotator cuff tear (definitely consider this if weakness is present) and impingement.

tests elicit pain, the patient likely has an impingement

On exam, the middle arc of the active abduction is

syndrome:

painful,

•

Neer test: Stabilize the scapula while passively lifting the arm in forward elevation toward the ear (forward flexion of glenohumeral joint).

•

Yocum test: While the patient touches the uninvolved

Diagnosis of impingement is clinical; imaging is usually

9 9

performed only when patients are refractory to therapy and require orthopedic referral.

r i h

Impingement syndrome Rotator cuff tear Frozen shoulder

Arthritis of the shoulder

extremes

are

painless.

Several

calcification/tear/tendonitis of the supraspinatus tendon or a fracture in the humeral

n U -

Hawkins test: With the patient's arm 90 degrees

shoulder, lift up on the flexed elbow.

the

tuberosity, where the

supraspinatus tendon attaches. Occasionally, pain is so

forward and the elbow in flexion, internally rotate the shoulder.

while

other problems can cause this painful middle arc; e.g.,

severe that the patient cannot accomplish any active

movement,

especially

abduction.

Passive

range

motion shows pain with abduction only.

Treat with range of motion exercises, NSAIDs, and ice. Consider intrabursal glucocorticoid injections if

infection has been ruled out and the patient does not respond to more conservative measures.

Rotator Cuff Abnormalities The rotator cuff is comprised of 4 muscles (teres minor,

infraspinatus, supraspinatus,

and subscapularis) that

stabilize the shoulder and allow the arm to elevate and rotate. Injuries or degeneration of the rotator cuff are the

Figure 6-4: Shoulder Antenor V1ew

Posterior

Figure 6-5: Shoulder Postenor V1ew

OFFICE ORTHOPEDICS

Treatment

most

tears

conservative:

nonnarcotic analgesics, and physical

rest,

therapy. Full

thickness tears in a healthy person are treated with surgery. Surgery is also considered when conservative •

treatment fails.

Name and describe 3 tests to assess shoulder impingement.

•

Compare and contrast the presentation of shoulder

Elbow

OA, impingement syndrome, subacromial bursitis,

Olecranon Bursitis

and rotator cuff injuries. •

This type of bursitis can be traumatic, septic, gouty, or

Olecranon bursitis is associated with which

secondary to RA. Traumatic bursitis ("student's elbow")

systemic diseases? •

is caused by chronic pressure. The bursa should be

How is lateral epicondylitis treated?

aspirated if there is any question about possible infection.

most common causes of shoulder pain. Some tears, even severe ones, can sometimes occur without pain-and manifest only as weakness! Consider a tear in patients who play overhead sports (e.g., baseball), have had shoulder trauma, are

50 years of age,

or have RA.

Pain with overhead reaches and night pain are classic features. The injury also can cause a subacromial bursitis, so always suspect a tear when patients present with bursitis features. Exam of partial tears demonstrates a positive painful arc test+/- weakness. The trick here is to determine whether apparent weakness is due to pain or a true muscle tear, because patients with pain guard their shoulder. (Lidocaine

injections

help

diagnostically

this

situation.) Another exam maneuver is to observe active

adduction: Patients who cannot adduct smoothly (called

the "drop-arm sign") may have a tear. The Neer and

9 ri 9

Hawkins tests help differentiate this from impingement syndrome.

Complete rotator cuff tear is very debilitating. It generally

G R

Treat uninfected bursitis with aspiration and NSAIDs or glucocorticoid injection. Treat septic bursitis with incision, drainage, and antibiotics. Oral antibiotics can be used for mild infections-IV is needed in severe

6-6.)

V d ti e n U inflammation. (See Figure Lateral Epicondylitis

"Tennis elbow" presents with tenderness and pain well localized to the front of the lateral epicondyle of the

elbow, where the extensor tendons of the forearm insert. Symptoms usually resolve spontaneously with decreased use of the elbow, although it may take 2 or more years.

Treatment: NSAIDs and splinting to reduce supination/

pronation provide

motion.

short-term

glucocorticoid

benefit,

but

injection

physical

may

therapy,

rehabilitation exercises, and activity modification are the mainstays of therapy.

Medial Epicondylitis

"Golfer's elbow" is similar to tennis elbow, but involves

involves separation of the supraspinatus tendon, but it

the "medial" epicondyle of the elbow. Treatment is the

may involve the adjacent subscapularis or infraspinatus

same.

tendons. These tendons blend with the shoulder joint

h ta

capsule, and a separation of the tendons generally involves the joint capsule. This allows "communication" between the shoulder joint and the subacromial bursa. Complete tears due to chronic repetitive injury usually occur in patients

years of age. Patients are unable

to abduct the arm due to weakness +/- pain, except by rotation of the scapula (shrugging the shoulder). Complete

Lateral epicondylitis

tears can also be caused by acute injuries from falls on an outstretched arm.

If you suspect a tear, start with plain radiographs because they can sometimes show you abnormalities in the positioning of the humeral head, acromion, and glenoid. MRI also can make the diagnosis, but abnormalities have to be clinically correlated because lots of asymptomatic

Lateral

people have tears visible on MRI. Olecranon bursitis Figure 6-6: Elbow Lateral V1ew

MedStudy

6-53

6-54

OFFICE ORTHOPEDICS

Wrist

adducted and clasped by the other fingers) reproduces the pain. Natural healing is very slow. Splinting, steroid

Carpal Tunnel Syndrome Carpal tunnel syndrome (CTS) presents as paresthesias and dysesthesias in the median nerve distribution (thumb through middle of 4'h finger) that are usually most bothersome during sleep. The symptoms can be reproduced by tapping on the volar aspect of the median nerve (Tine! sign) and/or forced flexion of the wrists for 30-60 seconds (Phalen test). Patients often describe tingling/numbness in the middle of the night where they would have to flick or shake out the hand.

injections, and NSAIDs can be beneficial for milder cases. Surgery, which is curative, should be reserved for patients with severe disability.

Hand

Dupuytren Contracture (Palmar Fibromatosis) This flexion contracture of the fingers is caused by thickening and contraction of the palmar fascia. The palmar fascia extends from the termination of the

Certain groups of patients are more susceptible; e.g.,

palmaris longus tendon on the wrist to the proximal and

pregnant women or those on oral contraceptives; dialysis

middle phalanges of the fingers. The ring and 5'h fingers

patients; and those with arthropathy associated with

are the most frequently affected. As the contraction

wrist synovitis (e.g., acromegaly,

and

RA).

Hypothyroidism, diabetes,

amyloidosis

are

also

associated

with CTS.

G R

progresses, you can see cord-like bands on the surface of the palm.

V d ti e

The cause is unknown, but these contractures are

Pain only in the shoulder or elbow is an atypical presentation. Nerve

conduction

studies

aid

the

diagnosis.

associated with a positive family history, epilepsy, diabetes,

alcoholism,

malignancies,

and

recurrent

occupational vibratory stimuli. Dupuytren contractures

Initial treatment consists of NSAlDs and a wrist splint

are primarily seen in Caucasians, usually men.

worn day and night for 3-4 weeks. Conduct carpal

Until recently, the cornerstone of treatment has been

tunnel release in patients with axonal (motor) loss,

surgical, but contractures tend to recur in the young.

weakness/atrophy of thenar eminence,

n U -

or in cases

In 2010, the FDA approved injectable collagenase

refractory to conservative treatments, such as splinting

clostridium histolyticum for the treatment of Dupuytren

or steroid injections.

contracture with a positive cord. This medication, which

Remember: CTS causes numbness in the thumb and 2"d, )rd , and 112 of the 4'h fingers, whereas cubital tunnel syndrome (entrapment of the ulnar nerve) causes numbness in the 4'h and 5'h fingers.

9 9

Ganglion Cyst

r i h

helps reduce the degree of contraction and improve

range of motion.

Trigger Finger

Ganglion cysts can occur at any joint or tendon sheath,

but they are most commonly found on the dorsum of the wrist at the scapholunate joint. The cyst is attached to a tendon sheath or the joint capsule. There is no communication between the inside of the joint capsule

contains 2 collagenases, is injected into the "cord" and

provides hydrolyzing activity on the collagen, which

and the interior of the ganglion. They are usually asymptomatic but may cause pain due to compression of a nerve or joint space. Ganglions generally are not treated, but temporary resolution may be provided by firm pressure or aspiration. The old remedy was slamming the ganglion with the family Bible! But this

When a finger gets "stuck" in flexion at the PIP joint, we call it "trigger finger" or digital tenosynovitis

stenosans. It is "unstuck" only with strong effort or with passive movement using the other hand-which causes significant pain. There is tenderness at the base of the finger (palmar aspect); often a tendon nodule can be felt. The cause is swelling of the flexor tendon and the opening of the flexor tendon sheath at the base of the finger. The middle or ring finger is most commonly affected.

Chronic

tenosynovitis

can

progress

Dupuytren contractures.

should be avoided because it may cause an inflammatory

Splinting and local steroid injections can help, but

response and recur. Definitive treatment is surgical.

a simple surgery is required to cure the condition. It consists of incising the mouth of the fibrous flexor sheath longitudinally.

De Quervain Tenosynovitis This is a chronic or subacute inflammation of the flexor tendons or the abductor pollicis longus tendon of the

Hip

thumb. It is characterized by pain and well-localized

Trochanteric Bursitis

tenderness over the styloid process of the distal radius. It is often caused by repetitive twisting of the wrist with certain motions, like wringing clothes. The Finkelstein test (forced ulnar motion of the wrist with the thumb

ÂŠ 2014

This bursitis is the most common cause of lateral thigh discomfort. Patients report "hip" pain when lying on the involved side, draping the involved leg over the non-involved limb, or bearing weight on the affected

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

OFFICE ORTHOPEDICS

cell disease, pregnancy, HIV/AIDS, Gaucher disease,

tr.k... a�·quiZ .•

hypercoagulable states, pancreatitis, lBO, and SLE.

•

Patients with femoral neck fractures or traumatic hip dislocations are especially susceptible because the blood

•

supply to the femoral head is disrupted.

Carpal tunnel syndrome affects which fingers? What about ulnar entrapment neuropathy?

•

AVN is best diagnosed early with an MRI showing

Which patients are at risk for AVN (osteonecrosis)

the

of the hip?

collapse (when plain radiographs may still be normal).

"crescent

sign"

signifying

subchondral

Be certain to image both hips with plain radiographs

Should MRI evaluation of AVN include one

and/or MRl because the risk of bilateral AVN is high,

or both hips? Why? •

classic

even if the patient is not symptomatic in the alternate hip

How does pain from hip OA differ from pain

(called "Stage

from trochanteric bursitis?

0").

Most patients with AVN eventually

need surgery. Early-stage disease can be treated with a

side. When asked specifically to point to the area of

revascularization

G R

procedure

(core

decompression

+!- bone graft), which may eliminate the need for hip

most intense pain, patients with bursitis will point to

replacement. Total joint replacement is the treatment of

the lateral aspect of the thigh over the greater trochanter

choice for late-stage disease.

(Figure

V d ti e n U

6-7 and Figure 6-8). This helps distinguish bursa

pain from true hip joint pain, which causes a point of maximum intensity in the groin (may radiate to the buttock). NSAIDs, local heat, PT, and/or glucocorticoid injections are very helpful.

HipOA Hip

osteoarthritis

presents as increased

pain with

use that is relieved with rest; the maximum point of

pain intensity is localized to the groin (Figure Figure

6-8),

6-7

and

a feature that distinguishes hip joint pain

from trochanteric bursitis. The pain also may refer to

Avascular Necrosis

the knee. Patients may complain of morning stiffness

Avascular necrosis (AVN), also called osteonecrosis, is a poorly understood condition resulting from an impaired blood supply to the bone. The compromised

blood supply can be due to trauma, certain medical conditions, medications/drugs, or idiopathic disease.

It most commonly affects the epiphysis (ends) of the femur (affecting the hip

9 ri 9

knee joints), followed by

the humerus. Patients on chronic glucocorticoids or

(< 30 minutes) and "gel phenomenon" (stiffness that

occurs after inactivity and resolves with use). Exam usually does not reveal any inflammation, but decreased range of motion and crepitus might be obvious.

Standing

"weight-bearing"

radiographs

show joint-space narrowing +/- subchondral sclerosis and/or osteophytes. In patients with typical pain and abnormal radiographs, no further imaging is necessary.

who abuse alcohol have a significant risk of AVN.

Medical conditions associated with AVN include sickle

h ta

Trochanteric

Inflammatory arthritis

Lateral

bursitis

Figure

MedStudy

6-7: Hip Antenor View

Figure

6-8: H ip Lateral View

6-55

6-56

OFFICE ORTHOPEDICS

Baker Cyst (Popliteal Cyst) Osteoarthritis of the hip and knee

This is simply a posterior herniation of the synovial cavity of the knee caused by a tense knee effusion (Figure

6-1 0). This forms a synovial, fluid-filled sac

in the midline behind the knee or in the upper calf. A Baker cyst usually occurs as a result of chronic arthritic conditions in which there is persistent synovial effusion (e.g., rheumatoid arthritis) or meniscal tears. If an arthritic patient with knee involvement presents with a painful swollen calf, suspect a ruptured Baker cyst causing pseudo-phlebitis. Phlebitis and deep venous thrombosis (DVT) also should be considered. Prognosis is usually good.

G R

On exam, the cyst can be palpated in the posterior knee when the knee is partially flexed. Or, have the patient stand while you look at the posterior knee for swelling. Occasionally, a Baker cyst can cause extrinsic venous

V d ti e

compression

phlebitis.

The

which can rule out DVT and visualize the cyst. Further imaging with MRl adds no useful information. Treatment

patients with

simulate

diagnostic test of choice is an ultrasound or LE Doppler,

Figure 6-9: Knee Anterior View Treat

that also can

education

on weight loss

is rest, NSAIDs,

and

treatment of the

and

underlying cause. If the cyst is very large or causes

nonnarcotic analgesics. Conservative measures should

significant pain, you can aspirate the knee (not the back

n U

be exhausted (especially weight loss, physical therapy,

of the knee!) and inject glucocorticoids. Refractory

and use of assist devices, such as canes) before referral

effusions may require surgical excision.

for total hip arthroplasty.

Knee Knee OA is discussed on page

Prepatellar Bursitis ("Housemaid's Knee" or "Clergyman's Knee")

6-22. (See Figure 6-9.)

9 9

r i h

This bursitis localizes pain over the patellar bursa and is caused by kneeling on hard surfaces (Figure

6-11 ).

If the symptoms worsen despite treatment with rest,

Prepatellar bursitis

Baker Cyst

Medial Figure 6-10: Lateral View of Baker Cyst

Figure 6-11: Knee Medial View

OFFICE ORTHOPEDICS

In contrast to secondary osteonecrosis, which usually requires surgical management (i.e., arthroplasty), SONK with small to mid-sized lesions has been shown to be responsive to nonoperative treatment. However, large •

•

What intervention can be used to treat

lesions may still require unicompartmental or total knee

a Baker cyst?

arthroplasty.

What is the specific presentation of pes anserine

Foot

bursitis?

Morton (Plantar) Neuroma

ice, NSAIDs, +/- steroid injection, consider a bacterial infection of the bursa, which may occur without an obvious source. If in doubt, aspirate the bursa and send for Gram stain and cultures.

This

benign

neuroma

causes

painful,

burning

paresthesias and tenderness in the interdigital webbing due to repeated nerve trauma. It is usually unilateral

G R

and most often appears between the 3'd and 4'h toes. It is much more common in women and thought to be

Pes Anserine Bursitis

related to high heels and tight fitting shoes. Palpation

This bursitis is caused by inflammation of the pes anserine bursa,

located over the medial aspect of

the proximal tibia 2 inches below the knee joint line (Figure 6-11 ). This is just proximal to the area where the 3 tendinous extensions of the gracilis, sartorius, and semi-tendinous muscles insert into the medial aspect of the tibial tuberosity. The symptom is pain in this area especially when climbing stairs. Pes anserine bursitis is associated with knee OA and obesity. Diabetes may be a predisposing factor. Remember to aspirate and exclude infection as a cause if there's any question about the source. Treatment is rest and analgesics, +/- steroid injection.

9 ri 9

Pigmented Villonodular Synovitis

Pigmented

villonodular

synovitis

(PVNS)

of the involved interspace produces sharp pain that often radiates into the toes, and squeezing the forefoot

V d ti e n U

often reproduces the patient's symptoms. Patients may

feel like they are standing on a pebble in their shoe. Treatment includes lowering the heel and wearing wider, soft-soled shoes with metatarsal arch support. Glucocorticoid injections may be helpful, and severe

cases may require surgical excision of the nerve. Plantar Fasciitis

This foot pain occurs most commonly in patients 40-60 years old, with increased incidence in runners

and ballet/aerobic dancers (Figure 6-12). It is generally idiopathic, benign, and self-limiting. The hallmark of

plantar fasciitis is a history of severe heel pain with the

first few steps in the morning or after other long periods without weight bearing.

idiopathic, monoarticular, benign synovial tumor that

Radiographs are usually not necessary, but can assist

causes recurrent hemarthrosis, usually of the knee in

in excluding diseases that present similarly, such as

young adults. Patients have recurrent bleeding into the knee, resulting in a darkly pigmented joint aspirate.

h ta

MRl is diagnostic with nodular intraarticular masses that

demonstrate low signal intensity. PVNS

responds

recurrent cases.

synovectomy

radiation

for Heel bone

Spontaneous Osteonecrosis of the Knee

Spontaneous osteonecrosis of the knee (SONK) most commonly affects the medial femoral condyle and may be the result of chronic mechanical stress or mild trauma in the elderly women.

Unlike

(60-70-year-olds),

secondary AVN

especially

(osteonecrosis)

plantar fascia

the knee, SONK is typically unilateral. There is no known etiology, although it seems to be associated with osteopenia and osteoarthritis. Weight-bearing pain is present initially on the medial aspect of the knee, and symptoms often resolve with conservative management, including protected weight bearing and analgesics. Do an MRI to exclude a tear in a meniscus.

MedStudy

Figure 6-12: Plantar Fasc1it1s

6-57

6-58

OFFICE ORTHOPEDICS

calcaneal stress fractures and Paget disease. Look for

By imaging, you are ruling out:

evidence of a spondyloarthropathy in any patient who

•Disk herniation

presents with plantar fasciitis.

• Spinal stenosis

Treatment is conservative: rest, NSAIDs, avoidance of

• Compression fracture

high heels, calf stretches, shoes with arch support, and

•Malignancy

heel inserts. Injection of mixed steroid/anesthetic can

•Infection

be done in refractory cases. Recurrent steroid injections should be avoided because they cause fat pad atrophy.

Muscle Strain More than 50% of adults experience at least I episode

LOW BACK PAIN

of back strain at some time. Classic presentation is

Overview

agonizing, lower back pain with a history of lifting a heavy object or making a sudden movement. Pain is

Acute lower back pam is one of the most common

G R V

increased when bending, lifting, turning, or coughing.

reasons why patients visit their primary care doctor. There

Sometimes initial pain is so severe that any movement of

are several causes of nonspecific, acute back pain. These

the torso is difficult.

include a moderately prolapsed disk, catching of the synovial membrane in a facet joint, transient subluxation

Physical exam typically reveals guarding of movement

with ligament strain, and basic muscle strain. Certainly

due to pain and no true muscle weakness or neurologic

worse diagnoses can cause lower back pain (e.g., spinal

deficit. Straight leg raises do not cause pain. This is a

stenosis, infection, or metastatic cancer), so your task is

clinical diagnosis. Know that imaging does not assist in

to differentiate the simple causes from ones that require

diagnosis of or treatment for muscle strain.

imaging and/or aggressive treatment.

t i n

General Approach to Lower Back Pain Evidence-based

practice

guidelines

d e

Most get better quickly: 40% in I week, 90% in 2 months. With acute back strain, continuing ordinary activities as tolerated leads to a more rapid recovery

issued

American College of Physicians in 2007, and updated in

U -

20II, focus on stratifying patients with back pain, based

on an initial assessment of historical risk factors for cancer/systemic disease ("red flags") and exam evidence of neurologic deficits.

9 9

than bed rest. Surgery is usually not required; studies

the

show that in non-emergent patients initially considered surgical candidates, conservative treatment is just as

effective as surgery in the long term.

Disk Herniation

Nonspecific lower back pain, sometimes called lumbago,

Herniation presents with local or radicular pain-and

is diagnosed when the patient gives the classic history

with weakness, if severe. Herniated disks are most

and has no red flags to suggest a more serious etiol

common at LS/S I because of progressive thinning of the

ogy. Treat with education (e.g., early mobility and heat

posterior longitudinal ligament. Central disk herniation

application) and analgesics of "proven benefit"

can cause saddle pain, anesthesia, and/or incontinence.

r i h

aminophen +/- NSAIDs.

acet

Classic disk pain is worse when sitting or bending and

Only patients who have neurologic deficits, a "serious"

better when standing or lying.

underlying condition (e.g., cancer), or other "red flags"

On exam, patients have pain when performing the

should receive urgent imaging. The main things you

straight leg raise. MRl without contrast is the test of

need to worry about when it comes to back pain red

choice for diagnosing a symptomatic herniated disk.

flags are infections (disci tis, osteomyelitis, paraspinal abscesses) and cancer (principally, prostate cancer and multiple myeloma).

Treat others conservatively

Long-term

outcomes

comparing

surgery

and

conservative management are equivalent. Neurologic deficits or intractable pain are indications for surgery

for

month and then

reassess with imaging reserved for refractory pain.

(i.e., microdiscectomy). See Neurology, Book 5, for more discussion of disk disease.

Underlying conditions that indicate a need for urgent

Spondylolysis and Spondylolisthesis

imaging: • Known cancer diagnosis

Spondylolysis is a defect in the isthmus of the neural arch

• Multiple risk factors for cancer

(pars interarticularis) of the

•Risks for osteomyelitis: Injection drug users,+TB

vertebra. This loss of bony continuity is visible, especially

S'h (rarely the 4th) lumbar

on the oblique view of a lumbar x-ray film.

screening test, recent TB exposure • Urinary retention

Although it was formerly thought to be congenital,

•Fecal incontinence

spondylolysis is now thought to be more likely secondary

•Progressive motor weakness

to a stress fracture during childhood.

MedStudy-Piease Report Copyright Infringements to copyright@medstudy.com

FOR FURTHER READING

FOR FURTHER READING [Guidelines in blue]

•

Name another disease that must be considered in a patient with plantar fasciitis.

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Which patients should get urgent imaging of the spine if they present with lower back pain?

of the antiribosomal P protein antibody. Arthritis Rheum. 1986;29:981-985. Bonfa E, Golombek SJ, et al. Association between lupus psy

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spondylolisthesis-a spontaneous subluxation (usually fmward) of one lumbar vertebra over another (usually anterior subluxation of

L4 over LS). Occasionally,

spondylolisthesis results in sciatica, but generally it does not affect the nerves of the cauda equina. Don't confuse these terms with spondylosis, which refers to osteoarthritis of the spine.

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Manchikanti L, Boswell MV, et al. Comprehensive evi dence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician. 2009 Jui-Aug; 12(4):699-802.

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